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ABSTRACT: Alcoholic fatty liver disease comprises alcoholic pure steatosis and alcoholic steatohepatitis. These diseases are prevalent, but their prognostic outcome is uncertain, particularly regarding the impact of hepatic inflammation. The paucity of data based on liver biopsy diagnoses contributes to this uncertainty.
To examine the cirrhosis and mortality risks of Danish men and women with biopsy-verified alcoholic pure steatosis or steatohepatitis.
In this registry-based historical cohort study we combined liver biopsy diagnoses with hospital discharge diagnoses from nationwide healthcare registries to identify all Danish citizens with alcoholic pure steatosis (N = 136) or alcoholic steatohepatitis (N = 58) during 1997-2008. We enrolled a reference cohort of 100 gender- and age-matched persons from the general population for each patient and compared cirrhosis and mortality risks through 2010.
The 5-year cirrhosis risks were 6.9% (95% CI: 3.4-12.2%) for patients with alcoholic pure steatosis and 16.0% (95% CI: 7.8-26.8%) for patients with alcoholic steatohepatitis, their 5-year mortality risks were 16.7% (95% CI: 11.3-24.2%) and 25.1% (95% CI: 15.7-38.9%), respectively. Patients with steatohepatitis had a higher liver-related mortality than patients with pure steatosis. In the reference cohort, the 5-year cirrhosis and mortality risks were 0.3% and 4.3%, respectively.
Patients with alcoholic fatty liver disease had markedly increased cirrhosis and mortality risks compared with a matched reference cohort. The cirrhosis risk was more than twice as high for the patients with steatohepatitis than for those with pure steatosis; and was higher for women than for men.
Alimentary Pharmacology & Therapeutics 04/2012; 35(11):1336-42. · 3.77 Impact Factor
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ABSTRACT: Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated. The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary-gonadal axis.
One hundred and sixteen (65 females) obese children with a median age of 12.3 (7-15) years were examined before and after a 10-week stay at a weight loss camp. Examination included anthropometry and fasting blood samples measuring plasma glucose, serum insulin, SHBG, DHEAS, testosterone, 17β-oestradiol, FSH and LH.
Body mass index (BMI) decreased (P<0.01), insulin sensitivity and SHBG increased (P<0.01), independent of gender and puberty. The changes in insulin sensitivity and the changes in SHBG correlated significantly (P<0.01) independent of gender, puberty and the changes in BMI. Testosterone increased in boys (P<0.01) and tended to decrease in girls (P=0.05, in girls after menarche (P=0.03)). FSH increased in boys and girls. LH increased in boys and was unchanged in girls.
During weight loss, insulin sensitivity and SHBG increased significantly in obese children, and the changes in insulin sensitivity and the changes in SHBG correlated significantly independent of gender, puberty and the changes in BMI. There was sexual dimorphism in the changes of testosterone, with the changes in boys towards increased virilisation and the changes in girls towards less virilisation.
European Journal of Endocrinology 12/2010; 163(6):895-900. · 3.42 Impact Factor
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ABSTRACT: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown.
To examine whether paracetamol-induced acute liver failure increases long-term mortality.
We followed up all transplant-free survivors of paracetamol-induced acute liver injury, hospitalized in a Danish national referral centre during 1984-2004. We compared age-specific mortality rates from 1 year post-discharge through 2008 between those in whom the liver injury led to an acute liver failure and those in whom it did not.
We included 641 patients. On average, age-specific mortality rates were slightly higher for the 101 patients whose paracetamol-induced liver injury had caused an acute liver failure (adjusted mortality rate ratio = 1.70, 95% CI 1.02-2.85), but the association was age-dependent, and no survivors of acute liver failure died of liver disease, whereas suicides were frequent in both groups. These observations speak against long-term effects of acute liver failure. More likely, the elevated mortality rate ratio resulted from incomplete adjustment for the greater prevalence of substance abuse among survivors of acute liver failure.
Paracetamol-induced acute liver failure did not affect long-term mortality. Clinical follow-up may be justified by the cause of the liver failure, but not by the liver failure itself.
Alimentary Pharmacology & Therapeutics 10/2010; 32(7):894-900. · 3.77 Impact Factor
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ABSTRACT: Objective To examine the risk of 30-day postoperative mortality from transurethral resection of the prostate (TURP) in patients with liver cirrhosis, who are reportedly at considerably increased perioperative risk.Patients and methods For the period 1 January 1977 to 31 December 1993, a population-based cohort was identified comprising Danish patients diagnosed with liver cirrhosis and a random sample of Danes also undergoing TURP. Logistic regression models were used to estimate the association between liver cirrhosis, age, type of admission, comorbidity and 30-day mortality.Results In a cohort of 23 133 patients with liver cirrhosis, 30 underwent TURP; 150 controls with no liver cirrhosis also underwent the same procedure. Of the patients with liver cirrhosis, 6.7% died within 30 days of TURP; the estimated adjusted odds ratio was 3.0 (95% confidence interval 0.4–22.9) for the 30-day postoperative mortality in patients with liver cirrhosis compared with patients without (mortality 2%). Advanced age, comorbidity and acute admission seemed to be associated with an increased postoperative mortality.Conclusion This study indicates that TURP in patients with liver cirrhosis was associated with increased mortality.
BJU International 07/2009; 87(3):183 - 186. · 2.84 Impact Factor
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ABSTRACT: Poisoning with weak analgesics is a major public health problem because of easy accessibility of the compounds; however, few studies have investigated their influence on subsequent suicide in the context of subjects' psychiatric status and other factors.
This nested case-control study was based on the entire Danish population including all 21,169 suicide cases and 423,128 matched population controls. Data on hospital admissions for poisoning and confounding factors were retrieved from national medical and administrative registries. Conditional logistic regression was used to compute relative risk.
A prior hospital admission for poisoning with weak non-opioid analgesics significantly increased the risk of subsequent suicide [crude incidence rate ratio (IRR) 24.7, 95% confidence interval (CI) 22.1-27.6], and the effect of paracetamol poisoning was substantially stronger than that of poisoning with salicylates or non-steroidal anti-inflammatory drugs (NSAIDs). This association could not be explained by confounding from socio-economic or psychiatric factors. The elevated risk was extremely high during the first week following the overdose (adjusted IRR 738.9, 95% CI 173.9-3139.1), then declined over time but still remained significantly high 3 years later (adjusted IRR 4.2, 95% CI 3.5-5.0). Moreover, a history of weak analgesic poisoning significantly interacted with a person's psychiatric history, increasing the risk for subsequent suicide substantially more for persons with no history of psychiatric hospitalization than did it for those with such a history.
A history of non-fatal poisoning with weak analgesics is a strong predictor for subsequent suicide. These results emphasize the importance of intensive psychiatric care of patients following overdose.
Psychological Medicine 05/2009; 39(11):1867-73. · 6.16 Impact Factor
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ABSTRACT: Colorectal cancer is a common cancer in the Nordic countries and 50% of the patients develop liver metastases. Liver resection may result in long term survival. Proper staging is therefore essential and CT is the standard imaging modality. We examined whether additional FDG-PET improves therapeutic management of patients with colorectal liver metastases.
Fifty-four consecutive patients were enrolled. Each patient had a treatment plan made based on our standard evaluation. The patients then had a PET scan and the treatment plan was re-evaluated, taking these results into account.
In 76% of the cases, PET did not change the treatment plan due to complete concordance with CT. In another 19% of the cases, the plan was altered due to finding of more liver lesions by PET than by CT (four patients), fewer or no liver lesions (three patients), and extrahepatic lesions not visible on CT (three patients). In 5% of the cases, non-concordance between PET and CT did not change the therapeutic plan.
Pre-treatment FDG-PET, used supplementary to CT, improved the treatment plan in one fifth of the patients with colorectal liver metastases.
Scandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society 02/2007; 96(3):209-13. · 1.03 Impact Factor
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ABSTRACT: Many cases of paracetamol poisoning are with suicidal intent, but the association between paracetamol poisoning and subsequent psychiatric disorder is unknown.
To examine the association between poisoning with paracetamol or other weak analgesics and subsequent psychiatric disorder.
The study was set in a nested case-control design and based on nationwide Danish registers. We identified all patients diagnosed with schizophrenia, affective disorder or eating disorder in 1994-1998 and matched population controls. We estimated the relative risk of these psychiatric disorders after admission for paracetamol or nonparacetamol poisoning, adjusting for income, employment and marital status.
We included 12,603 cases with psychiatric disorder, and 1.2% had a diagnosis of poisoning compared with 0.2% of the 252,060 matched population controls. Compared with those with no diagnoses of weak analgesic poisoning, the risk of schizophrenia increased 3.9-fold after paracetamol poisoning, and 2.0-fold after nonparacetamol poisoning. The risk of affective disorder increased 12.2-fold after paracetamol poisoning and 2.6-fold after nonparacetamol poisoning. The risk of eating disorder increased 5.0-fold after paracetamol poisoning, and 2.2-fold after nonparacetamol poisoning. The risk of a diagnosis of psychiatric disorder was very high immediately after poisoning and remained increased for more than 10 years.
Paracetamol poisoning is a strong risk marker for psychiatric disorder, particularly affective disorders.
Alimentary Pharmacology & Therapeutics 11/2005; 22(7):645-51. · 3.77 Impact Factor
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ABSTRACT: Pyogenic liver abscess is a life-threatening disease. Accurate data on incidence and prognosis are important, but scarce.
To examine changes in the incidence and 30-day mortality rate of patients with pyogenic liver abscess in Denmark.
Using nationwide administrative registers, we identified all patients diagnosed with pyogenic liver abscess in Denmark, 1977-2002, and their dates of death. We computed annual standardized incidence and 30-day mortality rates, and used Poisson regression to adjust gender-specific mortality rates for year-by-year differences in age at diagnosis.
We identified 1448 patients with pyogenic liver abscess, of whom 54% were men. The crude incidence rate for the entire study period was 11.8 per 1,000,000 for men and 9.7 per 1,000,000 for women. Between 1977 and 2002, the incidence rate increased from 6 to 18 per 1,000,000 for men and from 8 to 12 per 1,000,000 for women. The cumulative 30-day mortality rate was 15% for men and 23% for women. The adjusted 30-day mortality rate decreased from 40% for men and 50% for women to around 10% for both genders.
In this large nationwide study spanning a 26-year period, we found an increasing incidence rate and a decreasing mortality rate of pyogenic liver abscess. We believe that these changes are primarily explained by more sensitive diagnostic tools.
Alimentary Pharmacology & Therapeutics 06/2005; 21(10):1185-8. · 3.77 Impact Factor
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ABSTRACT: The case is presented of a 25-year-old Caucasian patient with Budd-Chiari syndrome due to membranous obstruction of the liver veins and inferior caval vein syndrome as a result of secondary hyperplasia of the caudate lobe of the liver, obstructing the caval vein. Diagnosis was established by intravascular pressure measurements, ultrasound examinations and caval and liver vein angiograms. Treatment consisting of stent placement in the outlet of a hepatic vein and subsequent transjugular intrahepatic porto-systemic shunt (TIPS) insertion via the caval vein was successful. After 34 months of follow-up the stents remain open and the patient is symptom free. This successful combination of stent placement and TIPS has not been described before. The case report is followed by a review of the literature on the use of angioplasty in short hepatic vein stenosis and TIPS in Budd-Chiari syndrome. It is concluded that angioplasty and TIPS are safe and efficient procedures to reduce liver engorgement and complications of portal hypertension in selected patients with Budd-Chiari syndrome.
Scandinavian Journal of Gastroenterology 10/2004; 39(10):1025-8. · 2.02 Impact Factor
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ABSTRACT: Patients with thrombosis of the portal or splenic vein may develop portal hypertension with bleeding from oesophageal or gastric varices. The relevant portal pressure cannot be measured by liver vein catheterization or transhepatic puncture of the portal vein because the obstruction is peripheral to the accessible part of the portal system.
Liver vein catheterization was combined with percutaneous splenic pressure measurement in 10 patients with portal or splenic vein thrombosis and no cirrhosis, and 10 cirrhotic patients without thrombosis. The splenic pressure was measured by percutaneous puncture below the curvature of the ribs with an angle of the needle to skin of 30 degrees in order to minimize the risk of cutting the spleen if the patient took a deep breath.
None of the patients in whom the described procedure was followed had complications. Pressure measurements in the spleen pulp and splenic vein were concordant. The pressure gradient across the portal venous system (splenic-to-wedged hepatic vein pressure) was -1.3 to 8.5 mmHg (median, 2.8 mmHg) in cirrhosis patients and 0-44 mmHg (median, 18 mmHg) in thrombosis patients, the variation reflecting various degrees of obstruction to flow in the portal venous system. Peripheral portal pressure (splenic-to-free liver vein pressure gradient) was 1.1-28 mmHg (median, 17 mmHg) in cirrhotic patients and 11-52 mmHg (median, 23 mmHg) in thrombosis patients.
Liver vein catheterization combined with percutaneous splenic pressure measurement is feasible in quantifying pressure gradient across a thrombosis of the portal/splenic vein and in quantifying portal pressure peripheral to this kind of thrombosis.
Scandinavian Journal of Gastroenterology 07/2004; 39(6):594-9. · 2.02 Impact Factor
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ABSTRACT: Water retention is a major clinical problem in patients with liver cirrhosis. Recent research suggests that renal aquaporins may be pathophysiologically involved in this condition. The aim of the present cross sectional study of patients with liver cirrhosis was to determine if 24 hour urinary excretion of renal aquaporin 2 (AQP2) differed from that of healthy control subjects and if such excretion was related to the severity of liver disease and to the patient's water balance.
Twenty four hour urinary excretion of AQP2 and free water clearance were measured in 33 stable cirrhosis patients on usual medication and in eight healthy subjects. AQP2 excretion, quantitated by immunoblotting, was eight times higher in cirrhosis patients than in controls (0.167 (0.270) U/day v 0.021 (0.017); p<0.05). Stratification according to clinical manifestations (Child- Pugh classes) revealed that it increased with the clinical severity of cirrhosis (class A 0.04 (0.04); class B 0.09 (0.16); class C 0.31 (0.35); p<0.05) but was not related to liver function, as measured by galactose elimination capacity. Excretion correlated inversely with free water clearance (rho=-0.57, p<0.01). It was higher in patients with oesophagogastric varices but not in those with ascites. Plasma vasopressin concentrations were not related to AQP2 excretion and there was no relation to dose or type of diuretic treatment.
Urinary AQP2 excretion was increased in patients with cirrhosis. Moreover, urinary AQP2 excretion increased with severity of cirrhosis in parallel with impairment of free water clearance. This suggests a functional association between increased AQP2 excretion and increased renal reabsorption of water in cirrhosis.
Gut 09/2003; 52(8):1194-9. · 10.11 Impact Factor
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ABSTRACT: To evaluate the influence of established liver cirrhosis on muscle strength and muscle contents of magnesium (Mg), potassium (K) and sodium, potassium pumps (Na,K-pumps) in chronic alcoholic patients.
An open cross-sectional study.
Forty consecutive chronic alcoholics (18 with cirrhosis and 22 without cirrhosis) admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, or to a collaborating alcoholism treatment centre, and 36 healthy control subjects.
Evaluation of participant's subjective physical ability and measurement of maximum isokinetic muscle strength and muscle mass, as well as measurements of Mg, K and Na,K-pumps in skeletal muscle.
Maximum isokinetic muscle strength and muscle mass were equally reduced in patients with and without cirrhosis (P < 0.01 all). In keeping with this, both groups of patients felt equally physically restricted. Muscle Mg was reduced to the same extent in the two groups of patients (by 12 and 9%, P < 0.001, both), whereas the muscle K content was only significantly lower in the cirrhotic patients (10%, P < 0.001). The muscle content of Na,K-pumps was reduced by 14%, (P < 0.01) in the cirrhotic patients and by 8% (P < 0.05) in the noncirrhotic patients.
Our alcoholic patients complained of physical disability, had reduced skeletal muscle mass, isokinetic muscle strength, content of muscle Mg and content of Na,K-pumps. There was no difference between patients with and without cirrhosis. It appears that it is the heavy alcohol intake, and not the cirrhosis per se, that is responsible for the observed defects.
Journal of Internal Medicine 03/2003; 253(3):359-66. · 5.48 Impact Factor
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Scandinavian Journal of Gastroenterology 12/2002; 37(11):1344. · 2.02 Impact Factor
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ABSTRACT: The hepatic venous pressure gradient (HVPG) is used to evaluate portal hypertension.
We measured HVPG in two separate liver veins in 169 liver vein catheterizations in 102 cirrhosis patients and in 27 patients with no liver disease (controls).
In the controls, the two measurements differed by 0.0 +/- 1.8 mmHg (mean +/- s, n = 27), upper 95% confidence limit 3.6 mmHg (mean + 2 s). HVPG ranged from -0.1 to 8.3 mmHg, upper 95% confidence limit 6.7 mmHg. In cirrhosis, the two measurements agreed within +/- 3.6 mmHg in 39%. In 61%, the measurements differed by 4-34 mmHg. In 35%, fluoroscopy demonstrated hepatic vein-to-hepatic-vein shunting in veins with low HVPG values. In some patients with HVPG measurements above 30 mmHg, Doppler ultrasound examination showed arterialization of the hepatic vasculature.
Our results demonstrate a hitherto unrecognized notable heterogeneity of the intrahepatic vasculature and HVPG measurements in cirrhosis. The presumption of interposition of non-flowing blood between the catheter tip and the portal system for the measurement of HVPG may thus be violated in about one-third of the cirrhosis cases because of abnormal outlet into hepatic venous shunts and in a minor fraction because of abnormal arterial inlet. In 26%, one measurement was below 12 mmHg, the other measurement above. If the HVPG had been measured in only one liver vein, 13% of the cases would have been classified in a lower risk group than appropriate according to the 12 mmHg concept of risk of bleeding from oesophageal varices.
Scandinavian Journal of Gastroenterology 09/2002; 37(8):960-4. · 2.02 Impact Factor
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ABSTRACT: To evaluate the muscle strength in relation to muscle contents of magnesium (Mg), potassium (K) and sodium, potassium (Na,K)-pumps in patients with alcoholic cirrhosis.
An open cross-sectional study.
Fifty-one consecutive patients with liver cirrhosis admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, and 28 age- and sex-matched healthy control subjects.
Biopsies of skeletal muscle were performed in patients and controls for measurements of Mg, K, and Na,K-pumps. Furthermore, maximum isokinetic knee extension and skeletal muscle mass were evaluated.
Muscle mass, muscle strength, muscle Mg and muscle K were substantially reduced in the patients (P < 0.01, all), and fell with increasing severity of the liver disease reflected in the Child-Pugh (C-P) class. Patients treated with spironolactone for 2 weeks or more, had increased muscle strength, muscle Mg and content of Na,K-pumps, compared with the rest of the patients (P < 0.05, all). In a multivariate analysis of the patients, skeletal muscle mass, muscle Mg and daily alcohol consumption (g) were independent predictors of isokinetic muscle strength (P < 0.05, all).
Patients with alcoholic liver cirrhosis showed considerably reduced muscle strength and muscle Mg was an independent predictor of muscle strength. Surprisingly, in the spironolactone treated patients, muscle weakness was less pronounced, possibly because of the action of spironolactone on muscle Mg, K and Na,K-pump content.
Journal of Internal Medicine 07/2002; 252(1):56-63. · 5.48 Impact Factor
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ABSTRACT: Catabolism and growth impairment are well known complications of chronic inflammatory bowel disease (CIBD). This may be caused by disease activity itself and/or the medical treatment, which may lead to changes in the growth hormone and insulinlike growth factor I (IGF-I) axis. Interest has focused on corticosteroids, as they are known to influence the growth hormone/IGF-I axis.
The aim of the present study was to examine changes in total and free IGF-I, IGF binding proteins (IGFBPs), and IGFBP-3 protease activity in 10 patients with severe acute activity in colon CIBD before and during high dose prednisolone treatment (1 wk) and 3 months tapering. Eight healthy subjects served as controls.
Total and free IGF-I were significantly reduced by 35% and 53%, respectively, before prednisolone treatment (p < 0.05), and free IGF-I remained reduced even by the end of the study period relative to controls (p < 0.05). IGFBP-3 was reduced by 16% before (p < 0.05), with normalization during prednisolone treatment and tapering relative to controls. There was no evidence of increase in IGFBP-3 protease activity. IGFBP-1 was increased before and tended also to be increased during prednisolone treatment and tapering.
Marked changes in serum total and free IGF-I and IGFBPs were demonstrated in patients with severe exacerbation of CIBD without complete normalization during high dose prednisolone treatment and tapering. These changes may partly be involved in the catabolism of active CIBD patients.
The American Journal of Gastroenterology 03/2002; 97(3):673-8. · 7.28 Impact Factor
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ABSTRACT: Cystatin C is a low molecular weight protein and the plasma level of cystatin C is mainly determined by glomerular filtration, making cystatin C an endogenous marker of glomerular filtration rate. The aim of the study was to elucidate the applicability of plasma cystatin C as a marker of renal function in patients with liver cirrhosis. Serum cystatin C and creatinine concentrations were compared with creatinine clearance. Thirty-six patients (14 females and 22 males aged between 33 and 81 years) with liver cirrhosis with normal to severely impaired kidney function were included. Plasma cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring Diagnostics) and plasma creatinine by an enzymatic method. Plasma levels of cystatin C and creatinine were found to increase with decreasing values of creatinine clearance. The reciprocal values of cystatin C and creatinine were compared with those for creatinine clearance revealing an r2 of 0.37 and 0.18, respectively. Comparison of the areas under the curves (AUC) of the non-parametric receiver-operating characteristic plots for plasma cystatin C (AUC=0.7364; SE=0.0929) and plasma creatinine (AUC=0.6309: SF=0.1028) revealed a significant difference between plasma cystatin C and plasma levels of creatinine (p-value=0.03). The results demonstrate that the diagnostic accuracy of plasma cystatin C was better than plasma creatinine in identifying liver cirrhotic patients with reduced glomerular filtration rate.
Scandinavian Journal of Clinical and Laboratory Investigation 02/2002; 62(2):129-34. · 1.38 Impact Factor
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ABSTRACT: Background/Aims: Long-term steroid treatment causes protein wasting. Liver contributes towards this by upregulating ureagenesis. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are anabolic agents with specific hepatic effects. It is unknown whether IGF-I alone and/or in combination with GH have any effect on established hepatic amino-N catabolism during long-term glucocorticoid treatment. Methods: We measured the spontaneous (UNSR) and the substrate standardized rate of urea nitrogen synthesis (STUNSR), N-balance and mRNA levels of urea cycle enzymes in controls (placebo) and four longterm steroid treated groups given (1) prednisolone 4 mg/kg/day during 28 days (St) (2) +GH 1 mg/kg/day from day 21-28 (StGH) (3) +IGF-I 1.5 mg/kg/day 21-28 (StIGF) (4) GH +IGF-I (StGHIGF). Results: Steroid induced weight loss was stepwisely reversed by IGF-I, GH and both. UNSR, STUNSR and mRNA levels of urea cycle enzymes in the liver increased markedly after steroid treatment, and was normalized after co-administration of GH and IGF-I. N-balance improved after GH and IGF-I administration. Conclusions: Our results expands the knowledge of beneficial effects of GH on short-term steroid catabolism to include effects of IGF-I and IGF-I combined with GH on long-term steroid catabolism. Both peptides prevent steroid induced hepatic protein wasting and thereby contribute towards whole body anabolism. The effect in vivo is probably due to an effect of the peptides on urea cycle enzyme mRNA.
Journal of Hepatology 01/2002; 35(6):700-6. · 9.26 Impact Factor
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ABSTRACT: Up-regulation of urea synthesis by amino acids and dietary protein intake may be impaired in patients with chronic pancreatitis (CP) due to the reduced glucagon secretion. Conversely, urea synthesis may be increased as a result of the chronic inflammation. The aims of the study were to determine urea synthesis kinetics in CP patients in relation to glucagon secretion (study I) and during an increase in protein intake (study II).
In study I, urea synthesis rate, calculated as urinary excretion rate corrected for accumulation in total body water and intestinal loss, was measured during infusion of alanine in 7 CP patients and 5 control subjects on spontaneous protein intake. The functional hepatic nitrogen clearance (FHNC), i.e. urea synthesis expressed independent of changes in plasma amino acid concentration, was calculated as the slope of the linear relation between urea synthesis rate and plasma alpha -amino nitrogen concentration. In study II, 6 of the patients of study I had urea synthesis and FHNC determined before and after a period of 14 days of supplementation with a protein-enriched liquid (dietary sequence randomized).
Study I: Alanine infusion increased urea synthesis rate by a factor of 10 in the control subjects, and by a factor of 5 in the CP patients (P<0.01). FHNC was 31.9+/-2.4 l/h in the control subjects and 16.5+/-2.0 l/h (P<0.05) in the CP patients. The glucagon response to alanine infusion (AUC) was reduced by 75 % in the CP patients. The reduction in FHNC paralleled the reduced glucagon response (r(2)=0.55, P<0.01). Study II: The spontaneous protein intake was 0.75+/-0.14 g/(kg x day) and increased during the high protein period to 1.77+/-0.12 g/(kg x day). This increased alanine stimulated urea synthesis by a factor of 1.3 (P<0.05), FHNC from 13.5+/-2.6 l/h to 19.4+/-3.1 l/h (P<0.01), and the glucagon response to alanine infusion (AUC) by a factor of 1.8 (P<0.05).
Urea synthesis rate and FHNC are markedly reduced in CP patients. This is associated with, and probably a result of, impaired glucagon secretion, and predicts a lower than normal postprandial hepatic loss of amino nitrogen. An increase in dietary protein intake increases alanine stimulated urea synthesis and FHNC by a mechanism that involves an increase in glucagon. This indicates that the low FHNC during spontaneous protein intake included an adaptation to the low protein intake, effectuated by a further decrease in glucagon secretion.
Clinical Nutrition 12/2001; 20(6):493-501. · 3.73 Impact Factor
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ABSTRACT: Patients with cirrhosis have low levels of coagulation factors, the most pronounced deficiency being that of FVII. This may compromise haemostasis during bleeding from ruptured oesophageal varices. The objective of this trial was to evaluate the effect of rFVIIa on prothrombin time in cirrhosis patients with ongoing variceal bleeding. Safety, including signs of DIC, was monitored.
The study is a single centre, open-label trial. Ten consecutive patients with known alcoholic cirrhosis and oesophageal variceal bleeding were included. The patients received routine treatment, including Terlipressin. Each patient received one i.v. injection of rFVIIa (80 microg/kg bw). The study observation time was 12 h per patient.
The mean age of the patients was 48 years (8 men and 2 women). The cirrhosis was classified as Child B in 5 patients and Child C in 5. At baseline, all patients had prothrombin time levels above the normal range, and all but one had FVII coagulation activity (FVII:C) levels below the normal range. rFVIIa normalized the prothrombin time in all patients within 30 min. The effect lasted for more than 4 h in 7 patients, and for about 2 h in the remaining 3 patients. Immediate bleeding control was obtained in all patients, and no patient died within the study time. There was no sign of DIC.
rFVIIa is effective in transiently reversing the prolonged prothrombin time in cirrhosis patients with haematemesis from varices. This indicates a potential of improving haemostasis and survival in patients with compromised coagulation due to liver disease.
Scandinavian Journal of Gastroenterology 11/2001; 36(10):1081-5. · 2.02 Impact Factor
