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Biomedical subjects

V Gülberg

Publications and source records attributed to V Gülberg.

At least 19 recordsLinked to original sources

[Renal impairment in liver diseases].

Renal failure in patients with liver disease is mostly none-organic: prerenal failure or hepatorenal syndrome (HRS). In addition there is organic renal failure, mostly acute tubular necrosis (ATN). In order to avoid functional renal failure cautious diuretic treatment as well as intravenous albumin substitution following paracentesis are pivotal. For prophylaxis of HRS patients with spontaneous bacterial peritonitis shall be given albumin infusions in addition to antibiotic treatment. Patients with HRS type I exhibit a very poor prognosis. Liver transplantation is the only established therapy with long-term success. To bridge the time to transplantation TIPS or terlipressin and albumin can be used.

Diagnosis, Differential↗

Endothelin and endothelin receptor antagonism in portopulmonary hypertension.

Portopulmonary hypertension (PPHT) is a rare but devastating complication in patients with portal hypertension, characterized by pulmonary arterial obliterative disease with a concomitant rise in pulmonary vascular resistance. A broad body of evidence has accumulated, indicating that endothelin (ET) peptides and their cognate receptors are causally involved in the pathophysiology of pulmonary arterial hypertension (PAH) owing to different aetiologies, including PPHT. In addition, the ET system may be involved in hepatic fibrotic remodelling and portal hypertension. Several experimental models have provided evidence that ET receptor antagonism may have therapeutic potential in PPHT. Initial experience has accumulated during the last 2 years, suggesting that targeting the ET system may have beneficial effects in the clinical setting. In these studies, the orally active, dual ET receptor antagonist bosentan improved pulmonary haemodynamics and functional capacity. These effects were sustained and occurred in the absence of adverse events. If these observations can be corroborated by controlled clinical trials, bosentan would offer several advantages over available therapies, which have major drawbacks owing to their invasive and demanding mode of application.

Administration, Oral↗

[Advances in therapy for ascites and hepatorenal syndrome].

Sequential diuretic treatment of ascites with spironolactone and furosemide is equivalent to initial combination therapy. Orally applicable vasopressin-V2-receptor antagonists are an interesting novel therapeutic approach for the elimination of free water. The therapeutic efficacy for patients with cirrhosis and ascites is currently being investigated in phase II trials. Following paracentesis of up to 6 liters volume, infusion of 3.5 % saline is as effective as 20 % albumin. Another trial confirms the superiority of TIPS for the treatment of massive ascites, also demonstrating survival benefit. Determination of leukocyte esterase activity with a simple stix method may be helpful for the rapid and easy diagnosis of spontaneous bacterial peritonitis. Patients with hepatorenal syndrome seem to benefit from a combination of terlipressin and albumin whereas the effect of albumin dialysis on survival remains to be proven.

Animals↗

Increased arterial compliance in cirrhosis is related to decreased arterial C-type natriuretic peptide, but not to atrial natriuretic peptide.

BACKGROUND: Increased arterial compliance (COMPart) has recently been described in patients with cirrhosis, particularly in advanced disease. The aim of the present study was to relate COMPart with arterial levels of the circulating natriuretic peptides: atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP), both of which are vasodilators. METHODS: Thirty-one patients with cirrhosis, 14 non-cirrhotic patients with circulatory disturbances of the ischaemic and hypertensive type, and 10 healthy controls were investigated during a haemodynamic examination. RESULTS: The patients with cirrhosis showed the well-known hyperdynamic circulation with elevated cardiac output, low arterial blood pressure, and reduced systemic vascular resistance. COMPart in the patients with cirrhosis (1.30 mL/mmHg) was significantly (P < 0.01) increased compared to that of non-cirrhotic patients (0.99 mL/mmHg) and controls (1.01 mL/mmHg). In the patients with cirrhosis, a significant inverse correlation was found between CNP and COMPart (r = -0.42, P < 0.01), but not between CNP and systemic vascular resistance (r = 0.31, P = 0.08). In the non-cirrhotic patients, CNP had a significant inverse correlation to COMPart (r = -0.68, P < 0.01) and a direct correlation to systemic vascular resistance (r = 0.62, P < 0.02). ANP was not significantly related to COMPart nor to systemic vascular resistance in any of the groups. CONCLUSION: The finding of an inverse relation between CNP and COMPart may suggest that a compensatory down-regulation of CNP occurs in patients with cirrhosis and other types of circulatory disorders when vasodilation persists. Regulation of large and small arteries by CNP may be different in cirrhosis. Arterial ANP is not related to properties of the large or small arteries.

Adult↗

TIPS or vasoconstrictors for the treatment of hepatorenal syndrome type 1--effect on survival?

HRS is a serious complication in patients with cirrhosis and ascites and associated with a poor prognosis unless liver transplantation can be performed. Two different types of HES are being differentiated according to the clinical presentation: while HRS type I is characterised by rapid deterioration of renal function indicated by a two-fold increase of serum creatinine to values above 2.5 mg/dl or a decrease of creatinine clearance to values below 20 ml/min, HRS type II shows moderately increased serum creatinine above 1.5 mg/dl remaining stable over a longer period. The most prominent circulatory alterations in patients with chronic liver disease comprise portal hypertension and peripheral (mainly splanchnic) arterial vasodilation. This leads to a decreased centrally effective blood volume in cirrhotic patients. As a consequence, activation of sodium- and volume-retaining neurohumoral systems such as the renin-angiotensin-aldosterone system and the sympathetic nervous system and a non-osmotic release of arginine-vasopressin can be observed. These neurohumoral alterations induce renal sodium and water retention which are responsible for accumulation of ascites and deterioration of renal function. Recent therapeutic strategies of the hepatorenal syndrome take into account these pathophysiologic considerations: whereas the transjugular intrahepatic portosystemic shunt lowers portal hypertension, infusion of vasoactive drugs increases systemic vascular resistance in cirrhotic patients. Several uncontrolled trials have reported a positive effect of these strategies on renal function. The present analysis of combined data from these reports shows that this positive effect on renal function also may improve survival of patients with HRS type I.

Hepatorenal Syndrome↗

Transjugular intrahepatic portosystemic shunting is not superior to endoscopic variceal band ligation for prevention of variceal rebleeding in cirrhotic patients: a randomized, controlled trial.

BACKGROUND: The aim of the present study was to compare the transjugular intrahepatic portosystemic shunt (TIPS) with variceal band ligation (VBL) in the prophylaxis of variceal rebleeding in patients with cirrhosis of the liver. METHODS: Fifty-four cirrhotic patients (21 Child-Pugh class A, 27 class B, 6 class C) were randomized to TIPS (n = 28) or VBL (n = 26) within 2 months after control of esophageal variceal hemorrhage. Statistical analysis was performed on the intention-to-treat principle. RESULTS: Mean follow-up was 2 years. Mortality risk at 1 and 2 years of follow-up was 7.8% +/- 5.3% and 19.9% +/- 8.8% in the TIPS group and 16.5% +/- 7.6% and 16.5% +/- 7.6% in the VBL group, respectively (n.s.); actuarial probability of remaining free from rebleeding was 83.7% +/- 77.4% and 71.4% +/- 10.4% in the TIPS group and 83.9% +/- 7.3% and 78.1% +/- 8.8% in the VBL group at 1 and 2 years, respectively (n.s.). Hepatic encephalopathy within 1 month after randomization was observed in 2 patients in the TIPS group and in 1 in the VBL group. CONCLUSION: TIPS is not superior to VBL in the prevention of variceal rebleeding. Furthermore, similar mortality rates in patients treated with TIPS or VBL negate TIPS as the preferred strategy for prevention of variceal rebleeding.

Endoscopy↗

Elevated arterial compliance in patients with cirrhosis is not related to arterial endothelin-1.

BACKGROUND: Patients with cirrhosis and portal hypertension have a hyperkinetic systemic circulation. A number of circulating vasoactive peptides, including endothelin-1 (ET-1), are elevated and, recently, increased arterial compliance has been described in these patients. The aim of the present study was to investigate a potential relation between altered arterial compliance and arterial ET-1 in patients with cirrhosis. As ET-1 may be manipulated by somastostatin, the study includes infusion of octreotide in a subset of patients. METHODS: A total of 67 patients with cirrhosis and 27 controls were studied during a haemodynamic investigation. Arterial ET-1 was determined by two different radioimmunoassays and arterial compliance was determined as the stroke volume/pulse pressure index. RESULTS: Arterial compliance was elevated by 32%-40% in the cirrhotic patients as compared to the controls (P < 0.005). Arterial ET-1 was elevated by 26%-170% in the cirrhotic patients (P<0.001). No significant relationships could be established between arterial compliance and arterial ET-1 (r = -0.15 to 0.23, ns). Intravenous bolus injection and infusion of octreotide (100 pg + 100 microg/h, n = 9) did not significantly change either arterial compliance or arterial ET-1. CONCLUSION: Both arterial compliance and arterial ET- I are substantially elevated in patients with cirrhosis, but there is no significant relation between arterial compliance and arterial ET- I in these patients.

Adult↗

Evaluation of serum cystatin C concentration as a marker of renal function in patients with cirrhosis of the liver.

BACKGROUND AND AIMS: Diagnosis of moderately impaired renal function is of particular importance in patients with cirrhosis of the liver. Whereas patients with a markedly impaired glomerular filtration rate can be diagnosed easily by elevated serum creatinine concentrations, moderately reduced renal function may be missed by this conventional parameter. Recently, cystatin C has been suggested as a sensitive marker of renal function, independent of sex or muscle mass. Therefore, the aim of this study was to investigate the value of serum cystatin C concentration for the detection of moderately impaired renal function. METHODS: Ninety seven in-hospital patients with cirrhosis and a 24 hour creatinine clearance of at least 40 ml/min were investigated and divided into group 1 (creatinine clearance > or = 70 ml/min; n = 55) and group 2 (creatinine clearance 40-69 ml/min; n = 42). RESULTS: Serum cystatin C concentrations (mean (SD): 1.31 (0.51) v 1.04 (0.34) mg/l (p = 0.008)) and creatinine concentrations (1.03 (0.52) v 0.86 (0.22) mg/100 ml (p=0.03)) were higher in group 2 than in group 1; there was no significant difference in urea concentrations. Receiver-operator characteristics (ROC) revealed a differential diagnostic advantage of cystatin C over creatinine and urea. At cut off concentrations of 1.0 mg/l, 0.9 mg/100 ml, and 28 mg/100 ml, respectively, cystatin C, creatinine, and urea exhibited 69%, 45%, and 44% sensitivity (p<0.05). As patients with a small muscle mass or reduced physical activity could be particularly prone to overestimation of their renal function, separate analyses were performed for the subgroups of female and Child-Pugh class C patients, respectively. In both groups, discrimination between patients with moderately impaired and normal renal function was best with cystatin C. In female patients, sensitivity of cystatin C (77.8%) was superior (p<0.05) to that of creatinine (38.9%) and urea (41.2%). In Child-Pugh C patients, the ROC curve was significantly better for cystatin C than for creatinine. CONCLUSIONS: Serum cystatin C determination could be a valuable tool in patients with cirrhosis, particularly with Child-Pugh class C or in female patients, for early diagnosis of moderately impaired renal function.

Biomarkers↗

A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.

BACKGROUND: In patients with cirrhosis and ascites, creation of a transjugular intrahepatic portosystemic shunt may reduce the ascites and improve renal function. However, the benefit of this procedure as compared with that of large-volume paracentesis is uncertain. METHODS: We randomly assigned 60 patients with cirrhosis and refractory or recurrent ascites (Child-Pugh class B in 42 patients and class C in 18 patients) to treatment with a transjugular shunt (29 patients) or large-volume paracentesis (31 patients). The mean (+/-SD) duration of follow-up was 45+/-16 months among those assigned to shunting and 44+/-18 months among those assigned to paracentesis. The primary outcome was survival without liver transplantation. RESULTS: Among the patients in the shunt group, 15 died and 1 underwent liver transplantation during the study period, as compared with 23 patients and 2 patients, respectively, in the paracentesis group. The probability of survival without liver transplantation was 69 percent at one year and 58 percent at two years in the shunt group, as compared with 52 percent and 32 percent in the paracentesis group (P=0.11 for the overall comparison, by the log-rank test). In a multivariate analysis, treatment with transjugular shunting was independently associated with survival without the need for transplantation (P=0.02). At three months, 61 percent of the patients in the shunt group and 18 percent of those in the paracentesis group had no ascites (P=0.006). The frequency of hepatic encephalopathy was similar in the two groups. Of the patients assigned to paracentesis in whom this procedure was unsuccessful, 10 received a transjugular shunt a mean of 5.5+/-4 months after randomization; 4 had a response to this rescue treatment. CONCLUSIONS: In comparison with large-volume paracentesis, the creation of a transjugular intrahepatic portosystemic shunt can improve the chance of survival without liver transplantation in patients with refractory or recurrent ascites.

Adult↗

Successful treatment of chronic Budd-Chiari syndrome with a transjugular intrahepatic portosystemic shunt.

Budd-Chiari syndrome is characterized by obstruction of the hepatic venous outflow tract. Therapeutic options for chronic Budd-Chiari syndrome are limited. We report the case of a 28-year-old woman who presented with recurrence of chronic Budd-Chiari syndrome with total obstruction of all major hepatic veins. Due to worsening liver function over the course of 1 year, she had to be listed for liver transplantation. Because of therapy-refractory ascites, declining renal function and severe esophageal varices, a transjugular intrahepatic portosystemic shunt (TIPS) was placed, planned as a bridge to transplantation. Following TIPS, a marked recovery of liver function could be observed, accompanied by disappearance of ascites, esophageal varices, and normalization of kidney function. Therefore, the patient could be removed from the waiting list for liver transplantation. This case demonstrates for the first time that the use of TIPS in chronic Budd-Chiari syndrome may result in marked recovery of liver function.

Adult↗

High-frequency oscillatory ventilation does not decrease endothelin release in lung-lavaged rabbits.

UNLABELLED: High-frequency oscillatory ventilation (HFO) has been shown to reduce lung injury and pulmonary arterial pressure (PAP). We hypothesized that HFO leads to decreased endothelin 1 (ET-1) and endothelin 3 (ET-3) release when compared to conventional mechanical ventilation (CMV) in lung-lavaged rabbits. DESIGN: Prospective, randomized, controlled animal study. In 26 adult New Zealand White Rabbits ventilated by CMV or HFO under hypoxemic and normoxemic conditions after lung lavage (CMV-hypo: n = 5; CMV-normo: n = 8; HFO-hypo: n = 7; HFO-normo: n = 6) we recorded systemic and PAP, measured blood gases, ET-1 and ET-3 and calculated intrapulmonary venous admixture during a 4-h experiment. ET-1 was significantly increased after lavage (p < 0.05) with no further increase until the end of the experiment. Neither pulmonary arterial nor systemic arterial ET-1 differed between CMV and HFO or between hypoxemia and normoxemia. Systemic arterial ET-3, however, was significantly higher in HFO-hypo than in the other two groups ventilated under normoxemic conditions at the end of the experiment (HFO-hypo vs. CMV-normo, p < 0.05; HFO-hypo vs. HFO-normo, p < 0.05). PAP showed a continuous increase in all groups (p < 0.05). We did not find any correlation between PAP and ET-1 or ET-3. Intrapulmonary venous admixture increased in animals ventilated under hypoxemic conditions, whereas it decreased after lung lavage in those ventilated under normoxemic conditions until the end of the experiment (HFO-normo, p < 0.05). CONCLUSIONS: This study suggests that HFO does not decrease ET-1 and ET-3 release compared to CMV in lung-lavaged rabbits. Hypoxemia, however, may increase ET-3 release from the lungs, leading to an increased intrapulmonary shunt.

Animals↗

Transjugular intrahepatic portosystemic shunt for cirrhosis and ascites: Effects in patients with organic or functional renal failure.

BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) is increasingly being used for treatment of patients with refractory ascites and functional renal failure. In contrast, organic renal disease is commonly considered a relative contraindication for TIPS placement. The aim of this pilot study was to investigate the effects of TIPS in patients with refractory ascites and organic or functional renal impairment. METHODS: A TIPS was placed for refractory or intractable ascites in 10 consecutive patients with liver cirrhosis and impaired renal function (serum creatinine > 1.5 mg/100 ml). Four of them had organic kidney disorders. Of these patients, three had moderate renal impairment, and one had end-stage renal disease and needed hemodialysis every other day. The other six patients had functional renal impairment due to the underlying liver disease. RESULTS: TIPS was effective in reducing ascites in 8 of 10 patients, including all patients with organic renal disease. Furthermore, after TIPS the renal function improved in all patients. Serum creatinine and serum urea levels decreased significantly from 1.8 +/- 0.1 to 1.5 +/- 0.1 mg/100 ml (P < 0.05) and from 107 +/- 13 to 78 +/- 14 mg/100 ml (P < 0.05), respectively. The renal function of the three patients with organic renal failure improved similarly, as observed in the six patients with functional renal failure. In the patient on hemodialysis, TIPS was effective in reducing the frequency of paracenteses. CONCLUSION: TIPS may be useful in patients with functional and in patients with organic renal disease, resulting in improvement of ascites and renal function.

Aged↗