Martin Roessle - Academia.edu (original) (raw)
Papers by Martin Roessle
Journal of radiology and imaging, Jan 2, 2018
Gastroenterology, May 1, 2013
(± SD) of 8.4 (±8.9) weeks from the time of viral breakthrough. Resistance patterns were detected... more (± SD) of 8.4 (±8.9) weeks from the time of viral breakthrough. Resistance patterns were detected in 6 of 8 (75%) patients and all patients had cross-resistance to boceprevir. All 4 patients with higher-level resistance patterns were genotype 1a. Both patients who tested sensitive were genotype 1b. Conclusion: Similar to findings in clinical trials, viral breakthrough with DAA for treatment of chronic HCV infection is associated with genotype 1a, advanced liver fibrosis, and prior null treatment response. Comparable patterns of resistance were also seen in clinical practice. In our study, however, a significant proportion of patients experienced viral breakthrough after completion of the DAA portion of triple therapy. More frequent virologic assessments during the PR treatment phase may be useful in a subset of "higher-risk" patients to expedite compliance with stopping rules and decrease unnecessary treatment burden. Treatment Response of Patients with Viral Breakthrough *Time between confirmation of viral breakthrough and testing of resistance **Any reduction in dosing of either ribavirin or interferon during treatment course ND = not detectable, defined as a viral load of less than 5 IU per millimeter; vBT = viral breakthrough RBV = ribavirin; IFN = interferon-alfa Higher-level resistance: V36M + R155K, Lower-level resistance: A156S, T54S All viral load results are expressed as IU per millimeter.
Gastroenterology, May 1, 2013
Gastroenterology, 2013
the first 12weeks 11.9% and 5.9% of the patients required dose modifications of ribavirin and peg... more the first 12weeks 11.9% and 5.9% of the patients required dose modifications of ribavirin and peginterferon alfa-2a, respectively and 2 (3.0%) and 17 (25.4%) patients had haemoglobin ,8.5 g/dL and ≥8.5 but ,10 g/dL respectively. Adverse events reported in at least 15% of patients included fatigue (52.9%), nausea (26.5%), headache (25.0%), skin disorder (23.5%), dysgeusia (19.1%), pruritus (19.1%), myalgia (17.6%), anaemia (16.2%) andarthralgia (16.2%). Conclusion: Real world experience with BOC plus peginterferon alfa2a/ribavirin in Germany show similar virological outcomes and side effects to the phase 3 trials. Week 8 HCV RNA values essential to determine suitability for reduced treatment duration were not collected in a significant proportion of patients.
Clinical Gastroenterology and Hepatology, 2019
BACKGROUND & AIMS: We studied the effects of diameter of covered, self-expandable, nitinol stents... more BACKGROUND & AIMS: We studied the effects of diameter of covered, self-expandable, nitinol stents on survival times of patients with a transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We collected data from 185 patients (median age, 55 y; 30% female) who received a covered nitinol stent, from February 2006 through September 2010, using the online multicenter German TIPS registry. TIPS were given to 107 patients for refractory ascites and to 78 patients for variceal bleeding. Patients at risk of hepatic encephalopathy (owing to advanced age, prior episodes) or liver failure (bilirubin level, >3 mg/dL), and bleeding patients receiving variceal embolization at TIPS, received 8-mm stents (n [ 53). The remaining patients received 10-mm stents (n [ 132). Eighty-one of the 10-mm stents were underdilated using 8-mm dilation balloons. Clinical and biochemical data were collected after TIPS placement at 1 month, 3 months, 6 months, 9 months, 1 year, and thereafter every 3 to 6 months. Groups were compared using propensity score analysis. RESULTS: Patients who received 8-mm stents survived significantly longer (34-26 mo) than patients who received 10-mm stents (18-19 mo), regardless of whether they were fully dilated or underdilated. When we compared 10-mm stents with or without underdilation, we found that a significantly higher proportion of patients who received underdilated stents survived for 1 month after TIPS placement (95% vs 84%; P [ .03), but not for 3 months (P [ .10). In multivariate analysis, 1-year mortality correlated with full dilation of the stent to 10 mm (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5) and with serum creatinine concentration at baseline (HR, 1.5; 95% CI, 1.0-1.7). Five-year mortality was associated with use of the 10-mm stents (HR, 1.8; 95% CI, 1.4-2.7) and baseline concentration of creatinine (HR, 1.3; 95% CI, 1.1-1.6). CONCLUSIONS: A smaller stent (nominal diameter of 8 mm, but not underdilation of a 10-mm stent) is associated with a prolonged survival compared with 10-mm stents, independent of liver-specific prognostic criteria.
Deutsche medizinische Wochenschrift (1946), Jan 4, 1998
Deutsche medizinische Wochenschrift (1946), Jan 22, 1995
Sclerotherapy was performed in a 52-year-old patient with alcoholic liver cirrhosis (Child-Pugh s... more Sclerotherapy was performed in a 52-year-old patient with alcoholic liver cirrhosis (Child-Pugh stage A) for recurrent bleeding from oesophageal varices. Half a year later he again was admitted to hospital because of recurrent passage of bloody stools. The cardiovascular status was stable; the liver was enlarged by 15 cm in the medioclavicular line. Endoscopy revealed several varices in the colon near the right flexure. One of the varices had an ulcer of 5 mm size. Duplex sonography revealed portal hypertension with cirrhosis of the liver and partial thrombosis of the main trunk of the portal vein without any sign of cavernous transformation. Because of the partial portal vein thrombosis it was decided to insert a transjugular intrahepatic portosystemic stent shunt. This obviated the thrombosis and lowered the portosystemic pressure gradient by 6.8%. With the shunt functioning well there were no further bleedings in the subsequent year. The only slightly invasive TIPS implantation i...
Annales de chirurgie, 1993
Transjugular intrahepatic portosystemic stent-shunt (TIPS) is a new technique in interventional r... more Transjugular intrahepatic portosystemic stent-shunt (TIPS) is a new technique in interventional radiology. This procedure is based on the creation of an intrahepatic channel between a main branch of the portal vein and an hepatic vein. A metallic stent is implanted to keep this shunt patent. From July 1990 to March 1992, 28 out of 32 patients with a history of gastric or esophageal variceal rebleeding, were treated by TIPS and followed for up to 20 months (mean 9.36 +/- 5.42). According to the Child Pugh's classification, 9 patients had class A cirrhosis, 17 class B and 6 class C. TIPS led to reduction of the portal pressure gradient by 57% and improvement of the portal blood flow by 250%. Early complications were: one technique-related death due to a medial stent implantation on the portal bifurcation (massive extrahepatic bleeding), other cases consisted of hemobilias (3 patients), intra-abdominal bleeding (1 patient) and gastrointestinal bleedings (4 patients). All of the com...
Der Radiologe, 1994
In 126 patients with liver cirrhosis treated electively with transjugular intrahepatic portosyste... more In 126 patients with liver cirrhosis treated electively with transjugular intrahepatic portosystemic stent shunt (TIPS) to prevent variceal rebleeding, the portosystemic pressure gradient decreased by 60%. In spite of this incomplete effect the risk for variceal rebleeding was still under 20% after 2 years. Only 1 patient died of variceal rebleeding. Shunt insufficiency occurred in 50%, mainly during the first year, but shunt function was restored in nearly all cases by radiologic intervention, i.e., redilatation or implantation of an additional stent. During the follow-up of 16 +/- 9 months, 21 patients (17%) died, one-third of them from progressive liver failure aggravated in 4 cases by severe drinking. De novo hepatic encephalopathy was observed in 10%, especially in older patients and patients with impaired liver function before TIPS. In such patients it is recommended that the shunt be dilated to 0.8 cm at most, and the TIPS procedure can be combined with transjugular embolizat...
Gastroenterology, 2007
Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shun... more Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shunt (TIPS) with large-volume paracentesis in cirrhotic patients with refractory ascites. Although all agree that TIPS reduces the recurrence rate of ascites, survival is controversial. The aim of this study was to compare the effects of TIPS and large-volume paracentesis in cirrhotic patients with refractory ascites by means of meta-analysis of individual patient data from 4 randomized controlled trials. The study population consisted of 305 patients: 149 allocated to TIPS and 156 to paracentesis. Cumulative probabilities of transplant-free survival and of hepatic encephalopathy (HE) were estimated by the Kaplan-Meier method and differences assessed by log-rank test. The total number of HE episodes per patient was also compared between TIPS and paracentesis. Tense ascites recurred in 42% of patients allocated to TIPS and 89% allocated to paracentesis (P < .0001). Sixty-five patients in ...
RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 1996
Klinische Wochenschrift, 1984
We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations o... more We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations of amino acids (AA) and ammonia in plasma and cerebrospinal fluid (CSF) and of the neurotransmitters norepinephrine, dopamine and 5-hydroxytryptamine (5-HT) as well as the 5-hydroxyindole acetic acid (5-HIAA) in CSF before and at the end of a 3-day period of treatment with infusions enriched with branched chain amino acids (BCAA). The subjects studied were 13 patients with alcoholic cirrhosis and hepatic encephalopathy stages 1-3 (n = 8) and stage 4 (n = 5). The patients in coma stages 1-3 recovered during the treatment (survivors), those in coma stage 4 died before the study period was finished (non-survivors). The data emerging from this study show: Alterations of AA concentrations are much more pronounced in the CSF than in the plasma. In the case of tryptophan the alterations in plasma and CSF were inverse. Before the treatment the CSF-plasma ratios of the concentrations of BCAA and aromatic amino acids (AAA) are increased reflecting an activated transport of both the BCAA and AAA through the blood-brain barrier. High dose BCAA nearly normalized CSF concentrations and CSF-plasma ratios of AAA assuming that the treatment brought about an effective competition of cerebral uptake between BCAA and AAA. The CSF concentrations of ammonia and glutamine decreased significantly during treatment while the plasma concentrations changed only moderately. As to the neurotransmitters, only the concentrations of 5-HT and its metabolite 5-HIAA correlated with the clinical picture and with the concentration of their precursor AA.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Hepatology, 2011
By both methods, depression was usually identified by Week 12, was related to CR2b dose, and was ... more By both methods, depression was usually identified by Week 12, was related to CR2b dose, and was frequent on 640ug CR2b and PEG2b (25-35%). The two lower doses of CR2b had lower rates of depression by both methods. Multivariate analysis showed BDI scores >20 (moderate depression) were associated with lower rates of viral negativity at end of treatment; SVR12 data appear to be equivalent for all four doses (data not shown). Conclusions: Depression was a common problem by Week 12 on PEG2b and on the highest dose of CR2b (640 ug) whether measured by clinic visits or BDI self-report. The lower rates of depression on 320ug and 480ug CR2b evident through Week 48 may offer an important advance in the treatment of HCV. Final 72-week results will be presented at the meeting.
Hepatology, 2004
Background & Aims: A 50% dysfunction rate at 1 year is one of the main drawbacks of the transjugu... more Background & Aims: A 50% dysfunction rate at 1 year is one of the main drawbacks of the transjugular intrahepatic portosystemic shunt procedure. Preliminary experimental and clinical studies suggest that the use of stents covered with polytetrafluorethylene could tremendously decrease this risk. Methods: Eighty patients with cirrhosis and uncontrolled bleeding (n ؍ 23), recurrent bleeding (n ؍ 25), or refractory ascites (n ؍ 32) were randomized to be treated by transjugular intrahepatic portosystemic shunts with either a polytetrafluorethylene-covered stent (group 1; 39 patients) or a usual uncovered prosthesis (group 2; 41 patients). Follow-up Doppler ultrasound was scheduled at day 7, at 1 month, and then every 3 months for 2 years. Angiography and portosystemic pressure gradient measurements were performed 6,12, and 24 months after the transjugular intrahepatic portosystemic shunt procedure and whenever dysfunction was suspected. Dysfunction was defined as a >50% reduction of the shunt at angiography or a portosystemic pressure gradient >12 mm Hg. Results: After a median follow-up of 300 days, 5 patients (13%) in group 1 and 18 (44%) in group 2 experienced shunt dysfunction (P < 0.0001). Clinical relapse occurred in 3 patients (8%) in group 1 and 12 (29%) in group 2 (P < 0.05). Actuarial rates of encephalopathy were 21% in group 1 and 41% in group 2 at 1 year (not significant). Estimated probabilities of survival were 71% and 60% at year 1 and 65% and 41% at 2 years in groups 1 and 2, respectively. Conclusions: The use of polytetrafluorethylene-covered prostheses improves transjugular intrahepatic portosystemic shunt patency and decreases the number of clinical relapses and reinterventions without increasing the risk of encephalopathy.
Hepatology, 1999
Intimal proliferation at the interface between prosthetic material and tissue is an intrinsic phe... more Intimal proliferation at the interface between prosthetic material and tissue is an intrinsic phenomenon of stenting and the major cause of insufficiency of the transjugular intrahepatic portosystemic shunt (TIPS). For its prevention, a randomized study was performed comparing standard heparin treatment with a combination of trapidil, a drug with anti-platelet-derived growth factor (PDGF) activity, and ticlopidine, a platelet aggregation inhibitor. Ninety patients with cirrhosis who received a transjugular shunt were randomized, and 84 patients completed the trial. Group 1 (n = 42) received a bolus of heparin (12 to 24 U/kg) at shunt placement, followed by 1 week of intravenous and 4 weeks of subcutaneous heparin treatment. Group 2 (n = 42) received the same heparin bolus, followed by a 1-day intravenous heparin treatment and a 6-month treatment with trapidil (400 mg/d) and ticlopidine (250 mg/d). Shunt function was assessed by duplex-sonography and angiography. Stenoses were classified according to their location as type 1 (within the stent) and type 2 (in the draining hepatic vein). The estimated rate of overall stenoses (intention-to-treat analysis) at 1 year showed a significant reduction in patients receiving trapidil and ticlopidine (group 2) as compared with heparin (33 vs. 57%; P =.047). There was no difference in the estimated 1-year rate of type 1 stenoses between the two groups, but there was a significant reduction in type 2 stenoses (group 1: 58%, group 2: 19%; P =.016). The treatment effect continued after withdrawal of the drugs and was accompanied by a decreased incidence of rebleeding. The study demonstrates that the incidence of type 2 stenosis of the transjugular shunt can be reduced by combined inhibition of platelet aggregation and PDGF activity. The findings may be of relevance not only for the transjugular shunt, but also for other stent applications, e.g., vascular and biliary, as well as for bypass and shunt surgery.
Gut, 2011
In a fluid flow network such as the portal system, flow and pressure variables can be calculated ... more In a fluid flow network such as the portal system, flow and pressure variables can be calculated in analogy to Ohm's law. Accordingly, the portal pressure depends on the hepatic resistance and the inflow through the splanchnic arterial bed. The latter has little importance in healthy liver because of the highly compliant vascular bed of the liver which passively adapts its diameter (ie, resistance) to flow through distension or shrinking of the organ.1 Thus, doubling of the portal flow results in only minimal changes in the portal pressure. With decreasing compliance of the liver during the development of cirrhosis, the flow increasingly determines the pressure. For instance, if compliance were to approach zero, doubling of the flow would result in doubling of the pressure. Consequently, only advanced cirrhosis may provide the physical basis for the flow to be the chicken, and not the egg. According to the ‘forward flow hypothesis’ portal hypertension is the result of both an increased hepatic resistance and an increased portal inflow.2 However, the increased hepatic resistance is seen more as an initiating event inducing an increased inflow which then causes most of the portal hypertension. The increased flow could be unrelated to the portal hypertension and could instead be the result of shunting of vasodilating substances causing a hyperdynamic state. The theory is mainly based on the rat model of portal vein constriction which showed 100% shunting and …
Alimentary Pharmacology and Therapeutics, 2006
Background Dysregulation of the cyclic guanosine 3¢,5¢ monophosphate-nitric oxide system is in pa... more Background Dysregulation of the cyclic guanosine 3¢,5¢ monophosphate-nitric oxide system is in part responsible for portal hypertension in cirrhosis. Aim To test the effects of inhibitors of phosphodiesterase-5 on portal haemodynamics. Methods To 18 healthy subjects and 18 patients with Child A liver cirrhosis, 10 mg of vardenafil, an inhibitor of phosphodiesterase-5, were administered orally. Doppler sonographic measurements of hepatic and splanchnic blood flow, systemic blood pressure and heart rate were recorded before, 1 h after, and 48 h after the application. Vardenafil plasma levels were determined after 1 h. In five patients, invasive registration of free and wedged hepatic vein pressure was performed. Results Portal venous flow increased in patients from 0.82 AE 0.30 L/min (mean AE s.d.) by 26% (CI: 16-37%, P ¼ 0.0004) and in healthy subjects from 0.75 AE 0.20 L/min (mean AE s.d.) by 19% (CI: 9-28%; P ¼ 0.0010). Celiac and hepatic artery resistivity indices rose significantly. Systemic blood pressure decreased slightly in patients. The wedged hepatic venous pressure gradient decreased in four of five patients with liver cirrhosis. Vardenafil plasma levels were higher in patients (14 AE 10 lg/L) than in healthy subjects (9 AE 6 lg/L; n.s.). Conclusions Inhibition of phosphodiesterase-5 increases portal flow and lowers portal pressure by a decrease in sinusoidal resistance and may be a novel therapeutic strategy for portal hypertension.
British Journal of Clinical Pharmacology, 1986
pressure in portopulmonary hypertension: a case report
Journal of radiology and imaging, Jan 2, 2018
Gastroenterology, May 1, 2013
(± SD) of 8.4 (±8.9) weeks from the time of viral breakthrough. Resistance patterns were detected... more (± SD) of 8.4 (±8.9) weeks from the time of viral breakthrough. Resistance patterns were detected in 6 of 8 (75%) patients and all patients had cross-resistance to boceprevir. All 4 patients with higher-level resistance patterns were genotype 1a. Both patients who tested sensitive were genotype 1b. Conclusion: Similar to findings in clinical trials, viral breakthrough with DAA for treatment of chronic HCV infection is associated with genotype 1a, advanced liver fibrosis, and prior null treatment response. Comparable patterns of resistance were also seen in clinical practice. In our study, however, a significant proportion of patients experienced viral breakthrough after completion of the DAA portion of triple therapy. More frequent virologic assessments during the PR treatment phase may be useful in a subset of "higher-risk" patients to expedite compliance with stopping rules and decrease unnecessary treatment burden. Treatment Response of Patients with Viral Breakthrough *Time between confirmation of viral breakthrough and testing of resistance **Any reduction in dosing of either ribavirin or interferon during treatment course ND = not detectable, defined as a viral load of less than 5 IU per millimeter; vBT = viral breakthrough RBV = ribavirin; IFN = interferon-alfa Higher-level resistance: V36M + R155K, Lower-level resistance: A156S, T54S All viral load results are expressed as IU per millimeter.
Gastroenterology, May 1, 2013
Gastroenterology, 2013
the first 12weeks 11.9% and 5.9% of the patients required dose modifications of ribavirin and peg... more the first 12weeks 11.9% and 5.9% of the patients required dose modifications of ribavirin and peginterferon alfa-2a, respectively and 2 (3.0%) and 17 (25.4%) patients had haemoglobin ,8.5 g/dL and ≥8.5 but ,10 g/dL respectively. Adverse events reported in at least 15% of patients included fatigue (52.9%), nausea (26.5%), headache (25.0%), skin disorder (23.5%), dysgeusia (19.1%), pruritus (19.1%), myalgia (17.6%), anaemia (16.2%) andarthralgia (16.2%). Conclusion: Real world experience with BOC plus peginterferon alfa2a/ribavirin in Germany show similar virological outcomes and side effects to the phase 3 trials. Week 8 HCV RNA values essential to determine suitability for reduced treatment duration were not collected in a significant proportion of patients.
Clinical Gastroenterology and Hepatology, 2019
BACKGROUND & AIMS: We studied the effects of diameter of covered, self-expandable, nitinol stents... more BACKGROUND & AIMS: We studied the effects of diameter of covered, self-expandable, nitinol stents on survival times of patients with a transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We collected data from 185 patients (median age, 55 y; 30% female) who received a covered nitinol stent, from February 2006 through September 2010, using the online multicenter German TIPS registry. TIPS were given to 107 patients for refractory ascites and to 78 patients for variceal bleeding. Patients at risk of hepatic encephalopathy (owing to advanced age, prior episodes) or liver failure (bilirubin level, >3 mg/dL), and bleeding patients receiving variceal embolization at TIPS, received 8-mm stents (n [ 53). The remaining patients received 10-mm stents (n [ 132). Eighty-one of the 10-mm stents were underdilated using 8-mm dilation balloons. Clinical and biochemical data were collected after TIPS placement at 1 month, 3 months, 6 months, 9 months, 1 year, and thereafter every 3 to 6 months. Groups were compared using propensity score analysis. RESULTS: Patients who received 8-mm stents survived significantly longer (34-26 mo) than patients who received 10-mm stents (18-19 mo), regardless of whether they were fully dilated or underdilated. When we compared 10-mm stents with or without underdilation, we found that a significantly higher proportion of patients who received underdilated stents survived for 1 month after TIPS placement (95% vs 84%; P [ .03), but not for 3 months (P [ .10). In multivariate analysis, 1-year mortality correlated with full dilation of the stent to 10 mm (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5) and with serum creatinine concentration at baseline (HR, 1.5; 95% CI, 1.0-1.7). Five-year mortality was associated with use of the 10-mm stents (HR, 1.8; 95% CI, 1.4-2.7) and baseline concentration of creatinine (HR, 1.3; 95% CI, 1.1-1.6). CONCLUSIONS: A smaller stent (nominal diameter of 8 mm, but not underdilation of a 10-mm stent) is associated with a prolonged survival compared with 10-mm stents, independent of liver-specific prognostic criteria.
Deutsche medizinische Wochenschrift (1946), Jan 4, 1998
Deutsche medizinische Wochenschrift (1946), Jan 22, 1995
Sclerotherapy was performed in a 52-year-old patient with alcoholic liver cirrhosis (Child-Pugh s... more Sclerotherapy was performed in a 52-year-old patient with alcoholic liver cirrhosis (Child-Pugh stage A) for recurrent bleeding from oesophageal varices. Half a year later he again was admitted to hospital because of recurrent passage of bloody stools. The cardiovascular status was stable; the liver was enlarged by 15 cm in the medioclavicular line. Endoscopy revealed several varices in the colon near the right flexure. One of the varices had an ulcer of 5 mm size. Duplex sonography revealed portal hypertension with cirrhosis of the liver and partial thrombosis of the main trunk of the portal vein without any sign of cavernous transformation. Because of the partial portal vein thrombosis it was decided to insert a transjugular intrahepatic portosystemic stent shunt. This obviated the thrombosis and lowered the portosystemic pressure gradient by 6.8%. With the shunt functioning well there were no further bleedings in the subsequent year. The only slightly invasive TIPS implantation i...
Annales de chirurgie, 1993
Transjugular intrahepatic portosystemic stent-shunt (TIPS) is a new technique in interventional r... more Transjugular intrahepatic portosystemic stent-shunt (TIPS) is a new technique in interventional radiology. This procedure is based on the creation of an intrahepatic channel between a main branch of the portal vein and an hepatic vein. A metallic stent is implanted to keep this shunt patent. From July 1990 to March 1992, 28 out of 32 patients with a history of gastric or esophageal variceal rebleeding, were treated by TIPS and followed for up to 20 months (mean 9.36 +/- 5.42). According to the Child Pugh's classification, 9 patients had class A cirrhosis, 17 class B and 6 class C. TIPS led to reduction of the portal pressure gradient by 57% and improvement of the portal blood flow by 250%. Early complications were: one technique-related death due to a medial stent implantation on the portal bifurcation (massive extrahepatic bleeding), other cases consisted of hemobilias (3 patients), intra-abdominal bleeding (1 patient) and gastrointestinal bleedings (4 patients). All of the com...
Der Radiologe, 1994
In 126 patients with liver cirrhosis treated electively with transjugular intrahepatic portosyste... more In 126 patients with liver cirrhosis treated electively with transjugular intrahepatic portosystemic stent shunt (TIPS) to prevent variceal rebleeding, the portosystemic pressure gradient decreased by 60%. In spite of this incomplete effect the risk for variceal rebleeding was still under 20% after 2 years. Only 1 patient died of variceal rebleeding. Shunt insufficiency occurred in 50%, mainly during the first year, but shunt function was restored in nearly all cases by radiologic intervention, i.e., redilatation or implantation of an additional stent. During the follow-up of 16 +/- 9 months, 21 patients (17%) died, one-third of them from progressive liver failure aggravated in 4 cases by severe drinking. De novo hepatic encephalopathy was observed in 10%, especially in older patients and patients with impaired liver function before TIPS. In such patients it is recommended that the shunt be dilated to 0.8 cm at most, and the TIPS procedure can be combined with transjugular embolizat...
Gastroenterology, 2007
Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shun... more Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shunt (TIPS) with large-volume paracentesis in cirrhotic patients with refractory ascites. Although all agree that TIPS reduces the recurrence rate of ascites, survival is controversial. The aim of this study was to compare the effects of TIPS and large-volume paracentesis in cirrhotic patients with refractory ascites by means of meta-analysis of individual patient data from 4 randomized controlled trials. The study population consisted of 305 patients: 149 allocated to TIPS and 156 to paracentesis. Cumulative probabilities of transplant-free survival and of hepatic encephalopathy (HE) were estimated by the Kaplan-Meier method and differences assessed by log-rank test. The total number of HE episodes per patient was also compared between TIPS and paracentesis. Tense ascites recurred in 42% of patients allocated to TIPS and 89% allocated to paracentesis (P < .0001). Sixty-five patients in ...
RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 1996
Klinische Wochenschrift, 1984
We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations o... more We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations of amino acids (AA) and ammonia in plasma and cerebrospinal fluid (CSF) and of the neurotransmitters norepinephrine, dopamine and 5-hydroxytryptamine (5-HT) as well as the 5-hydroxyindole acetic acid (5-HIAA) in CSF before and at the end of a 3-day period of treatment with infusions enriched with branched chain amino acids (BCAA). The subjects studied were 13 patients with alcoholic cirrhosis and hepatic encephalopathy stages 1-3 (n = 8) and stage 4 (n = 5). The patients in coma stages 1-3 recovered during the treatment (survivors), those in coma stage 4 died before the study period was finished (non-survivors). The data emerging from this study show: Alterations of AA concentrations are much more pronounced in the CSF than in the plasma. In the case of tryptophan the alterations in plasma and CSF were inverse. Before the treatment the CSF-plasma ratios of the concentrations of BCAA and aromatic amino acids (AAA) are increased reflecting an activated transport of both the BCAA and AAA through the blood-brain barrier. High dose BCAA nearly normalized CSF concentrations and CSF-plasma ratios of AAA assuming that the treatment brought about an effective competition of cerebral uptake between BCAA and AAA. The CSF concentrations of ammonia and glutamine decreased significantly during treatment while the plasma concentrations changed only moderately. As to the neurotransmitters, only the concentrations of 5-HT and its metabolite 5-HIAA correlated with the clinical picture and with the concentration of their precursor AA.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Hepatology, 2011
By both methods, depression was usually identified by Week 12, was related to CR2b dose, and was ... more By both methods, depression was usually identified by Week 12, was related to CR2b dose, and was frequent on 640ug CR2b and PEG2b (25-35%). The two lower doses of CR2b had lower rates of depression by both methods. Multivariate analysis showed BDI scores >20 (moderate depression) were associated with lower rates of viral negativity at end of treatment; SVR12 data appear to be equivalent for all four doses (data not shown). Conclusions: Depression was a common problem by Week 12 on PEG2b and on the highest dose of CR2b (640 ug) whether measured by clinic visits or BDI self-report. The lower rates of depression on 320ug and 480ug CR2b evident through Week 48 may offer an important advance in the treatment of HCV. Final 72-week results will be presented at the meeting.
Hepatology, 2004
Background & Aims: A 50% dysfunction rate at 1 year is one of the main drawbacks of the transjugu... more Background & Aims: A 50% dysfunction rate at 1 year is one of the main drawbacks of the transjugular intrahepatic portosystemic shunt procedure. Preliminary experimental and clinical studies suggest that the use of stents covered with polytetrafluorethylene could tremendously decrease this risk. Methods: Eighty patients with cirrhosis and uncontrolled bleeding (n ؍ 23), recurrent bleeding (n ؍ 25), or refractory ascites (n ؍ 32) were randomized to be treated by transjugular intrahepatic portosystemic shunts with either a polytetrafluorethylene-covered stent (group 1; 39 patients) or a usual uncovered prosthesis (group 2; 41 patients). Follow-up Doppler ultrasound was scheduled at day 7, at 1 month, and then every 3 months for 2 years. Angiography and portosystemic pressure gradient measurements were performed 6,12, and 24 months after the transjugular intrahepatic portosystemic shunt procedure and whenever dysfunction was suspected. Dysfunction was defined as a >50% reduction of the shunt at angiography or a portosystemic pressure gradient >12 mm Hg. Results: After a median follow-up of 300 days, 5 patients (13%) in group 1 and 18 (44%) in group 2 experienced shunt dysfunction (P < 0.0001). Clinical relapse occurred in 3 patients (8%) in group 1 and 12 (29%) in group 2 (P < 0.05). Actuarial rates of encephalopathy were 21% in group 1 and 41% in group 2 at 1 year (not significant). Estimated probabilities of survival were 71% and 60% at year 1 and 65% and 41% at 2 years in groups 1 and 2, respectively. Conclusions: The use of polytetrafluorethylene-covered prostheses improves transjugular intrahepatic portosystemic shunt patency and decreases the number of clinical relapses and reinterventions without increasing the risk of encephalopathy.
Hepatology, 1999
Intimal proliferation at the interface between prosthetic material and tissue is an intrinsic phe... more Intimal proliferation at the interface between prosthetic material and tissue is an intrinsic phenomenon of stenting and the major cause of insufficiency of the transjugular intrahepatic portosystemic shunt (TIPS). For its prevention, a randomized study was performed comparing standard heparin treatment with a combination of trapidil, a drug with anti-platelet-derived growth factor (PDGF) activity, and ticlopidine, a platelet aggregation inhibitor. Ninety patients with cirrhosis who received a transjugular shunt were randomized, and 84 patients completed the trial. Group 1 (n = 42) received a bolus of heparin (12 to 24 U/kg) at shunt placement, followed by 1 week of intravenous and 4 weeks of subcutaneous heparin treatment. Group 2 (n = 42) received the same heparin bolus, followed by a 1-day intravenous heparin treatment and a 6-month treatment with trapidil (400 mg/d) and ticlopidine (250 mg/d). Shunt function was assessed by duplex-sonography and angiography. Stenoses were classified according to their location as type 1 (within the stent) and type 2 (in the draining hepatic vein). The estimated rate of overall stenoses (intention-to-treat analysis) at 1 year showed a significant reduction in patients receiving trapidil and ticlopidine (group 2) as compared with heparin (33 vs. 57%; P =.047). There was no difference in the estimated 1-year rate of type 1 stenoses between the two groups, but there was a significant reduction in type 2 stenoses (group 1: 58%, group 2: 19%; P =.016). The treatment effect continued after withdrawal of the drugs and was accompanied by a decreased incidence of rebleeding. The study demonstrates that the incidence of type 2 stenosis of the transjugular shunt can be reduced by combined inhibition of platelet aggregation and PDGF activity. The findings may be of relevance not only for the transjugular shunt, but also for other stent applications, e.g., vascular and biliary, as well as for bypass and shunt surgery.
Gut, 2011
In a fluid flow network such as the portal system, flow and pressure variables can be calculated ... more In a fluid flow network such as the portal system, flow and pressure variables can be calculated in analogy to Ohm's law. Accordingly, the portal pressure depends on the hepatic resistance and the inflow through the splanchnic arterial bed. The latter has little importance in healthy liver because of the highly compliant vascular bed of the liver which passively adapts its diameter (ie, resistance) to flow through distension or shrinking of the organ.1 Thus, doubling of the portal flow results in only minimal changes in the portal pressure. With decreasing compliance of the liver during the development of cirrhosis, the flow increasingly determines the pressure. For instance, if compliance were to approach zero, doubling of the flow would result in doubling of the pressure. Consequently, only advanced cirrhosis may provide the physical basis for the flow to be the chicken, and not the egg. According to the ‘forward flow hypothesis’ portal hypertension is the result of both an increased hepatic resistance and an increased portal inflow.2 However, the increased hepatic resistance is seen more as an initiating event inducing an increased inflow which then causes most of the portal hypertension. The increased flow could be unrelated to the portal hypertension and could instead be the result of shunting of vasodilating substances causing a hyperdynamic state. The theory is mainly based on the rat model of portal vein constriction which showed 100% shunting and …
Alimentary Pharmacology and Therapeutics, 2006
Background Dysregulation of the cyclic guanosine 3¢,5¢ monophosphate-nitric oxide system is in pa... more Background Dysregulation of the cyclic guanosine 3¢,5¢ monophosphate-nitric oxide system is in part responsible for portal hypertension in cirrhosis. Aim To test the effects of inhibitors of phosphodiesterase-5 on portal haemodynamics. Methods To 18 healthy subjects and 18 patients with Child A liver cirrhosis, 10 mg of vardenafil, an inhibitor of phosphodiesterase-5, were administered orally. Doppler sonographic measurements of hepatic and splanchnic blood flow, systemic blood pressure and heart rate were recorded before, 1 h after, and 48 h after the application. Vardenafil plasma levels were determined after 1 h. In five patients, invasive registration of free and wedged hepatic vein pressure was performed. Results Portal venous flow increased in patients from 0.82 AE 0.30 L/min (mean AE s.d.) by 26% (CI: 16-37%, P ¼ 0.0004) and in healthy subjects from 0.75 AE 0.20 L/min (mean AE s.d.) by 19% (CI: 9-28%; P ¼ 0.0010). Celiac and hepatic artery resistivity indices rose significantly. Systemic blood pressure decreased slightly in patients. The wedged hepatic venous pressure gradient decreased in four of five patients with liver cirrhosis. Vardenafil plasma levels were higher in patients (14 AE 10 lg/L) than in healthy subjects (9 AE 6 lg/L; n.s.). Conclusions Inhibition of phosphodiesterase-5 increases portal flow and lowers portal pressure by a decrease in sinusoidal resistance and may be a novel therapeutic strategy for portal hypertension.
British Journal of Clinical Pharmacology, 1986
pressure in portopulmonary hypertension: a case report