-
1.
The single-dose pharmacokinetics of alitretinoin and its metabolites are not significantly altered in patients with cirrhosis.
Thyssen, JP, Vester, L, Grønhøj Larsen, C, Smidt, K, Jakobsen, P, Hansen, SH, Vind-Kezunovic, D, Gluud, LL, Grønhøj Larsen, F
The British journal of dermatology. 2014;(2):408-14
Abstract
BACKGROUND Alitretinoin (9-cis-retinoic acid, Toctino(®) ) has been marketed recently for oral therapy for chronic hyperkeratotic hand eczema. As alitretinoin is highly lipophilic and metabolized mainly in the liver, it is currently considered to be contraindicated in patients with liver disease. However, the pharmacokinetics and metabolism of alitretinoin have not been studied in these patients. OBJECTIVES To study the single-dose pharmacokinetics and metabolism of alitretinoin and its metabolites in patients with cirrhosis following oral administration. METHODS Eight patients with cirrhosis and eight matched volunteer healthy controls were given a single 30-mg oral dose of alitretinoin. Blood and urine samples were collected during the following 24-h study period. Samples were analysed for alitretinoin and for known metabolites using reverse-phase high-performance liquid chromatography. The pharmacokinetics were then evaluated using standard noncompartmental models. RESULTS No significant differences were found between healthy controls and patients with cirrhosis when analysing the pharmacokinetic parameters of alitretinoin and its metabolites. Thus, the mean half-lives of alitretinoin were 5·3 and 5·6 h (P = 0.733) and the oral clearances were 1·92 and 1·39 L h(-1) kg(-1) (P = 0·243) in the patient group and the healthy control group, respectively. CONCLUSIONS The metabolism and pharmacokinetics of alitretinoin following oral administration of the recommended dose of 30 mg for the treatment of severe hand eczema were similar in patients with cirrhosis and in healthy controls. If indicated, alitretinoin can be used in these patients with careful and close monitoring.
-
2.
The effectiveness of the treatment of octreotide on chylous ascites after liver cirrhosis.
Zhou, DX, Zhou, HB, Wang, Q, Zou, SS, Wang, H, Hu, HP
Digestive diseases and sciences. 2009;(8):1783-8
Abstract
Octreotide is a crucial drug used for treating patients with chylous ascites; however, there have been few reports related to octreotide that are being used in cirrhotic patients. Thus, this thesis is designed to determine the effects of octreotide on patients with chylous ascites after liver cirrhosis. Eight patients were diagnosed with chylous ascites, on the basis of laboratory findings on ascites samples, between January 2003 and May 2008. Octreotide was given to the six patients, while the remaining two were treated as a control. All patients had persistent peritoneal drainage with the quantity and quality of the drainage fluid observed once every other day. All the necessary care was individually given to the patients during the therapy. All patients properly received combined therapy including a low-fat and low-sodium diet, and diuretic and peritoneal drainage. The volume of the peritoneal drainage was reduced to zero in one of the six patients who received octreotide therapy, while the other five had the drainage volumes decreased from 2,000 to 50 ml with a clear appearance and negative qualitative analysis of chyle. For those two patients who did not receive octreotide therapy, the conditions of peritoneal drainage seldom changed both from the qualitative and quantitative aspects. In conclusion, Octreotide, along with combined therapy, can rapidly relieve portal hypertension and reduce triglyceride levels in ascites. It appears to be an effective therapy available for the treatment of chylous ascites caused by liver cirrhosis.
-
3.
Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial.
Seeff, LB, Curto, TM, Szabo, G, Everson, GT, Bonkovsky, HL, Dienstag, JL, Shiffman, ML, Lindsay, KL, Lok, AS, Di Bisceglie, AM, et al
Hepatology (Baltimore, Md.). 2008;(2):605-12
-
-
Free full text
-
Abstract
Herbal products, used for centuries in Far Eastern countries, are gaining popularity in western countries. Surveys indicate that persons with chronic hepatitis C (CHC) often use herbals, especially silymarin (milk thistle extract), hoping to improve the modest response to antiviral therapy and reduce side effects. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial, involving persons with advanced CHC, nonresponders to prior antiviral therapy but still willing to participate in long-term pegylated interferon treatment, offered the opportunity to examine the use and potential effects of silymarin. Among 1145 study participants, 56% had never taken herbals, 21% admitted past use, and 23% were using them at enrollment. Silymarin constituted 72% of 60 herbals used at enrollment. Among all participants, 67% had never used silymarin, 16% used it in the past, and 17% used it at baseline. Silymarin use varied widely among the 10 participating study centers; men were more frequent users than women, as were non-Hispanic whites than African Americans and Hispanics. Silymarin use correlated strongly with higher education. No beneficial effect of silymarin was found on serum alanine aminotransferase or hepatitis C virus (HCV) RNA levels. Univariate analysis showed significantly fewer liver-related symptoms and better quality-of-life parameters in users than nonusers, but after reanalysis adjusted for covariates of age, race, education, alcohol consumption, exercise, body mass index, and smoking, only fatigue, nausea, liver pain, anorexia, muscle and joint pain, and general health remained significantly better in silymarin users. In conclusion, silymarin users had similar alanine aminotransferase and HCV levels to those of nonusers but fewer symptoms and somewhat better quality-of-life indices. Because its use among these HALT-C participants was self-motivated and uncontrolled, however, only a well-designed prospective study can determine whether silymarin provides benefit to persons with chronic hepatitis C.
-
4.
Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance.
Bahr, MJ, Ockenga, J, Böker, KH, Manns, MP, Tietge, UJ
American journal of physiology. Endocrinology and metabolism. 2006;(2):E199-206
Abstract
The adipokine resistin has been implicated in obesity and insulin resistance. Liver cirrhosis is associated with decreased body fat mass and insulin resistance. We determined plasma resistin levels in 57 patients with cirrhosis, 13 after liver transplantation, and 30 controls and correlated these with hemodynamic as well as hepatic and systemic metabolic parameters. Patients with cirrhosis had, dependent on the clinical stage, an overall 86% increase in resistin levels (P < 0.001) with hepatic venous resistin being higher than arterial levels (P < 0.001). Circulating resistin was significantly correlated with plasma TNF-alpha levels (r = 0.62, P < 0.001). No correlation was observed between resistin and hepatic hemodynamics, body fat mass, systemic energy metabolism, and the degree of insulin resistance. However, plasma resistin in cirrhosis was negatively associated with hepatic glucose production (r = -0.47, P < 0.01) and positively with circulating free fatty acids (FFA; r = 0.40, P < 0.01) and ketone bodies (r = 0.48, P < 0.001) as well as hepatic ketone body production (r = 0.40, P < 0.01). After liver transplantation, plasma resistin levels remained unchanged, whereas insulin resistance was significantly improved (P < 0.01). These data provide novel insights into the role of resistin in the pathophysiological background of a catabolic disease in humans and also indicate that resistin inhibition may not represent a suitable therapeutic strategy for the treatment of insulin resistance and diabetes in patients with liver cirrhosis.
-
5.
Octreotide in liver cirrhosis: a salvage for variceal bleeding can be a gunshot for kidneys.
Güney Duman, D, Tüney, D, Bilsel, S, Benli, F, Karan, S, Avsar, E, Ozdogan, O, Tözün, N
Liver international : official journal of the International Association for the Study of the Liver. 2005;(3):527-35
Abstract
BACKGROUND The renal effects of octreotide, used for bleeding esophageal varices in cirrhosis, are controversial. METHODS Fourteen cirrhotic patients (Child-Pugh; A/B/C: 1/12/1) were enrolled. Plasma nitrite and endothelin (ET) levels, urinary nitrite output, free water clearance (FWC) and fractional excretion of filtered sodium (FENa) were measured and renal Doppler ultrasound was carried out. Octreotide was infused at a rate of 0.75 microg/kg/h for 3 h after a bolus of 0.75 microg/kg body weight. All the parameters were reevaluated during octreotide administration while the patients acted as their own controls. RESULTS Octreotide induced significant reductions in urinary nitrite, FENa and FWC. Plasma ET levels increased (baseline: 6.7 pg/ml, octreotide: 8.4 pg/ml), whereas the plasma nitrite level did not change significantly after octreotide infusion. Overall, no significant change in renal resistive index (RRI) could be demonstrated on Doppler after octreotide administration. However, patients with elevated baseline RRI values had significantly more deterioration in FWC and FENa compared with patients with normal RRI in response to octreotide. CONCLUSION A marked decrease in FENa, FWC and urinary nitrite output, together with a significant increase in plasma ET level in response to octreotide, may indicate renal dysfunction in cirrhotic patients. This deleterious renal effect of octreotide may be more enhanced in patients with elevated baseline RRI.
-
6.
Long term effects of phlebotomy on biochemical and histological parameters of chronic hepatitis C.
Yano, M, Hayashi, H, Wakusawa, S, Sanae, F, Takikawa, T, Shiono, Y, Arao, M, Ukai, K, Ito, H, Watanabe, K, et al
The American journal of gastroenterology. 2002;(1):133-7
Abstract
OBJECTIVES There is considerable evidence that iron is a risk factor for liver injury in chronic hepatitis C. Known as iron reduction therapy, phlebotomy reduces serum ALT activity. This effect might continue with maintenance phlebotomy and result in slower progression of liver fibrosis. METHODS We examined the biochemical parameters and liver histology of patients with chronic hepatitis C treated by maintenance phlebotomy. For biochemical evaluation, 25 patients were treated by initial phlebotomy to reduce serum ferritin levels to 10 ng/ml or less and then observed for 5 yr with maintenance phlebotomy to maintain the iron-deficient state. For histological evaluation, liver biopsies were performed before and after the study period in 13 of the patients. Thirteen patients who were virological nonresponders to interferon alone and had undergone second liver biopsies after more than 3 yr served as histological controls. RESULTS Serum aminotransferase levels were decreased significantly by initial phlebotomy and remained at the same levels during the study period (p < 0.05). The grading scores were improved significantly in the study group (p < 0.05) and unchanged in the controls. The staging scores remained unchanged in the study group but were increased in the controls (p < 0.005). Disease progression was significantly different between the two groups (p < 0.05). CONCLUSIONS These results suggest that phlebotomy with maintenance lowers serum aminotransferase levels, improves liver inflammation, and suppresses the progression of liver fibrosis in chronic hepatitis C.
-
7.
Effect of the somatostatin analogue lanreotide on meal-stimulated portal blood flow in patients with liver cirrhosis.
Schiedermaier, P, Harrison, P, Arthur, M, Grandt, D, Sutton, R, Drewe, J, Larsen, F, Sieber, C, ,
Digestion. 2002;(1):56-60
Abstract
BACKGROUND Lanreotide, a new long-acting somatostatin analogue, has been shown to inhibit the meal-stimulated increase of splanchnic blood flow in healthy volunteers. To date, similar data in patients with liver cirrhosis have not been available. We have examined the effect of lanreotide compared with placebo on meal-stimulated portal blood flow in patients with liver cirrhosis using Doppler ultrasound. METHODS 20 cirrhotic patients (placebo n = 12, lanreotide n = 8) with proven portal hypertension were studied after an overnight fast. Lanreotide, at a dose of 100 microg/h, was infused intravenously over 7 h after a 1-hour basal period. In parallel to the intravenous infusion, a liquid test meal (Ensure plus, 1.5 kcal/min) was perfused for 7 h through an intraduodenal tube at a rate of 3 ml/min. Blood pressure, heart rate and portal vein blood flow (PVF, ml/min, Doppler technique) were determined at regular intervals. RESULTS Baseline PVF amounted to 725 +/- 182 ml/min in the placebo and to 917 +/- 252 ml/min in the lanreotide group (n.s.). The meal-stimulated increase in PVF was blunted by lanreotide (AUC, % x min): 62,709.6 +/- 6,817 (placebo) vs. 45,237 +/- 2,507 (lanreotide), p < 0.05. Lanreotide also blunted the postprandial increase in heart rate for the first 2 h of meal perfusion. CONCLUSIONS Because of potent inhibition of postprandial splanchnic hyperemia in patients with liver cirrhosis, lanreotide may be useful in the treatment of complications of portal hypertension.
-
8.
Beneficial effect of a traditional herbal medicine (inchin-ko-to) in postoperative biliary atresia patients.
Kobayashi, H, Horikoshi, K, Yamataka, A, Lane, GJ, Yamamoto, M, Miyano, T
Pediatric surgery international. 2001;(5-6):386-9
Abstract
Inchin-ko-to (ICKT) prevents Fas-mediated liver injury. This study evaluates the effect of ICKT on conventional markers of liver function (LF) and liver fibrosis in 18 postoperative biliary atresia (BA) patients aged 3 to 23 years with elevated glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyl transpeptidase (gammaGTP) but normal serum total bilirubin (T-Bil) levels. ICKT (0.15 g/kg per day) was administered orally for 1 year. Serum GOT, GPT, gammaGTP, total bile acids (TBA), and T-Bil as markers of LF and hyaluronic acid (HA), prolyl hydroxylase (PH), procollagen III peptide (PIIIP), and type IV collagen as markers of liver fibrosis were measured before and after treatment in each patient and compared statistically. All patients tolerated ICKT well, and there were no side effects. The percentage of subjects who improved after ICKT was 45% for serum GOT, 72% for GPT, 72% for gammaGTP, 72% for TBA, 67% for HA, 40% for PH, 50% for PIIIP, and 23% for type IV collagen. Changes in the mean values of all serum markers were statistically significant (P < 0.01). It is concluded that long-term administration of ICKT in postoperative BA patients improves liver status as assessed by markers of LF and fibrosis.
-
9.
Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety).
Federle, MP, Chezmar, JL, Rubin, DL, Weinreb, JC, Freeny, PC, Semelka, RC, Brown, JJ, Borello, JA, Lee, JK, Mattrey, R, et al
Journal of magnetic resonance imaging : JMRI. 2000;(1):186-97
Abstract
The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.
-
10.
Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging.
Federle, M, Chezmar, J, Rubin, DL, Weinreb, J, Freeny, P, Schmiedl, UP, Brown, JJ, Borrello, JA, Lee, JK, Semelka, RC, et al
Journal of magnetic resonance imaging : JMRI. 2000;(5):689-701
Abstract
The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.