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Nicole M F van Gerven,
Ynto S de Boer,
Antonie Zwiers,
Bart van Hoek,
Karel J van Erpecum,
Ulrich Beuers, Henk R van Buuren,
Joost P H Drenth,
Jannie W den Ouden,
Robert C Verdonk,
Ger H Koek,
Johannes T Brouwer,
Maureen M J Guichelaar,
Jan M Vrolijk,
G Kraal,
Chris J J Mulder,
Carin M J van Nieuwkerk,
Gerd Bouma
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ABSTRACT: BACKGROUND & AIMS: Single nucleotide polymorphisms (SNP) in the Cytotoxic T lymphocyte antigen-4 gene (CTLA-4) have been associated with several autoimmune diseases including autoimmune Hepatitis (AIH). In this chronic idiopathic inflammatory liver disease, conflicting results have been reported on the association with a SNP at position +49 in the CTLA-4 gene in small patient cohorts. Here, we established the role of this SNP in a sufficiently large cohort of AIH patients. METHODS: The study population consisted of 672 AIH patients derived from academic and regional hospitals in the Netherlands and was compared with 500 controls selected from the 'Genome of the Netherlands' project cohort. Genotype frequencies were assessed by PCR for patients and by whole genome sequencing for controls. RESULTS: No significant differences in allele frequencies were found between patients and controls (G Allele: 40% vs 39%, P = 0.7). Similarly, no significant differences in genotype frequencies between patients and controls were found. Finally, there was no relation between disease activity and the G allele or AG and GG genotypes. CONCLUSION: The Cytotoxic T Lymphocyte Antigen-4 +49 A/G polymorphism does not represent a major susceptibility risk allele for AIH in Caucasians and is not associated with disease severity at presentation.
Liver international: official journal of the International Association for the Study of the Liver 03/2013; · 3.82 Impact Factor
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ABSTRACT: BACKGROUND & AIMS: It remains unclear when anticoagulant therapy should be given in patients with non-cirrhotic portal vein thrombosis (PVT). Aim of this study was to assess the effect of anticoagulation on recurrent thrombotic events and gastrointestinal bleeding in non-cirrhotic PVT patients. METHODS: Retrospective study of all patients with non-cirrhotic PVT (n=120), seen at our hospital from 1985 to 2009. Data were collected by systematic chart review. RESULTS: Sixty-six of the 120 patients were treated with anticoagulants. Twenty-two recurrent thrombotic events occurred in 19 patients. Overall thrombotic risk at one, five and ten years was 4%, 8% and 27%, respectively. Seventy-four percent of all recurrent thrombotic events occurred in patients with a prothrombotic disorder. Anticoagulant therapy tended to lower the risk of recurrent thrombosis (HR 0.2 p=0.1), yet the only significant predictor of recurrent thrombotic events was presence of a prothrombotic disorder (HR 3.1 p=0.03). In thirty-seven patients 83 gastrointestinal bleeding events occurred. Rebleeding risk at one, five and ten years was 19%, 46% and 49%, respectively. Anticoagulation therapy (HR 2.0 p=<0.01) was a significant predictors of (re)bleeding. Anticoagulation therapy had no effect on severity of gastrointestinal bleeding. Poor survival was associated with recurrent thrombotic events (HR 3.1 p=0.02), whereas bleeding (HR 1.6 p=0.2) and anticoagulant treatment (HR 0.5 p=0.2) had no significant effect on survival. CONCLUSIONS: In non-cirrhotic PVT patients recurrent thrombotic events are mainly observed in patients with underlying prothrombotic disorders. Anticoagulation therapy tends to prevent recurrent thrombosis but also significantly increases the risk of gastrointestinal bleeding. © 2013 International Society on Thrombosis and Haemostasis.
Journal of Thrombosis and Haemostasis 01/2013; · 5.73 Impact Factor
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Nicole M F van Gerven,
Bart J Verwer,
Birgit I Witte,
Bart van Hoek,
Minneke J Coenraad,
Karel J van Erpecum,
Ulrich Beuers, Henk R van Buuren,
Rob A de Man,
Joost P H Drenth,
Jannie W den Ouden,
Robert C Verdonk,
Ger H Koek,
Johannes T Brouwer,
Maureen M J Guichelaar,
Chris J J Mulder,
Karin M J van Nieuwkerk,
Gerd Bouma
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ABSTRACT: BACKGROUND AND AIMS: Current treatment strategies in autoimmune hepatitis (AIH) include long-term treatment with corticosteroids and/or azathioprine. Here we determined risk of relapse after drug withdrawal in patients in long-term remission and factors associated with such a relapse. METHODS: A total of 131 patients (out of a cohort including 844 patients) from 7 Academic and 14 regional centres in the Netherlands were identified in whom treatment was tapered after at least two years of clinical and biochemical remission. Relapse was defined as ALT (Alanine-aminotransferase) levels three times above the upper limit of normal and loss of remission as a rising ALT necessitating the reinstitution of drug treatment. RESULTS: During follow-up, 61 (47%) patients relapsed and 56 (42%) had a loss of remission. In these 117 patients, 60 patients had fully discontinued medication whereas 57 patients were still on a withdrawal scheme. One year after drug withdrawal 59% of patients required retreatment, increasing to 73% and 81% after two and three years, respectively. Previous combination therapy of corticosteroids and azathioprine, a concomitant autoimmune disease and younger age at time of drug withdrawal were associated with an increased risk of a relapse. Subsequent attempts for discontinuation after initial failure in 32 patients resulted inevitably in a new relapse. CONCLUSION: This retrospective analysis indicates that loss of remission or relapse occurs in virtually all patients with AIH in long term remission when immunosuppressive therapy is discontinued. These findings indicate a reluctant attitude towards discontinuation of immunosuppressive treatment in AIH patients.
Journal of Hepatology 09/2012; · 9.26 Impact Factor
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ABSTRACT: BackgroundFatigue is a major clinical problem in many patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis
(PSC). An effective treatment has not been defined. Recently, a large proportion of patients with these diseases was found
to have symptoms of depression. Because fatigue is a frequent symptom of depression and there is some evidence that treatment
with an antidepressant improves fatigue in patients with fibromyalgia, we hypothesised that the antidepressant fluvoxamine
might improve fatigue related to PBC and PSC.
MethodsFatigued patients were randomised to receive fluvoxamine (75 mg BID) or placebo for a six-week period. Fatigue and quality
of life were quantified using a visual analogue scale, the Fisk Fatigue Severity Scale, the Multidimensional Fatigue Inventory
and the SF-36.
ResultsSeventeen and 16 patients were allocated to fluvoxamine and placebo, respectively. There was no statistically significant
beneficial effect of fluvoxamine on fatigue or quality of life. The median VAS scores in the fluvoxamine and placebo groups
were 7.40 and 7.45 at day 0, 6.9 and 7.15 at day 14, 7.45 and 7.65 at day 42 and 7.8 and 8.0 four weeks after treatment discontinuation.
ConclusionWe found no evidence for a beneficial effect of fluvoxamine on fatigue in these patients with cholestatic liver disease and
severe chronic fatigue.
BMC Gastroenterology 04/2012; 4(1):1-8. · 2.42 Impact Factor
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Andreas E Kremer,
Remco van Dijk,
Pamela Leckie,
Frank G Schaap,
Edith M M Kuiper,
Thomas Mettang,
Katrin S Reiners,
Ulrike Raap, Henk R van Buuren,
Karel J van Erpecum,
Nathan A Davies,
Christian Rust,
Andreas Engert,
Rajiv Jalan,
Ronald P J Oude Elferink,
Ulrich Beuers
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ABSTRACT: Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus. In this study, we highlight that increased serum ATX levels are specific for pruritus of cholestasis, but not pruritus of uremia, Hodgkin's disease, or atopic dermatitis. Treatment of patients with cholestasis with the bile salt sequestrant, colesevelam, but not placebo, effectively reduced total serum bile salts and fibroblast growth factor 19 levels, but only marginally altered pruritus intensity and ATX activity. Rifampicin (RMP) significantly reduced itch intensity and ATX activity in patients with pruritus not responding to bile salt sequestrants. In vitro, RMP inhibited ATX expression in human HepG2 hepatoma cells and hepatoma cells overexpressing the pregnane X receptor (PXR), but not in hepatoma cells in which PXR was knocked down. Treatment of severe, refractory pruritus by the molecular adsorbents recirculation system or nasobiliary drainage improved itch intensity, which, again, correlated with the reduction of ATX levels. Upon reoccurrence of pruritus, ATX activity returned to pretreatment values. Conclusion: Serum ATX activity is specifically increased in patients with cholestatic, but not other forms of, systemic pruritus and closely correlates with the effectiveness of therapeutic interventions. The beneficial antipruritic action of RMP may be explained, at least partly, by the PXR-dependent transcriptional inhibition of ATX expression. Thus, ATX likely represents a novel therapeutic target for pruritus of cholestasis. (HEPATOLOGY 2012).
Hepatology 04/2012; 56(4):1391-400. · 11.66 Impact Factor
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ABSTRACT: Fully-covered self expandable metal stents (fcSEMSs) are an alternative to progressive plastic stenting for the treatment of benign biliary strictures (BBS) with the prospect of a higher treatment efficacy and the need for fewer ERCPs, thereby reducing the burden for patients and possibly costs. Key to this novel treatment is safe stent removal.
To investigate the feasibility and safety of stent removal of a fcSEMS with a proximal retrieval lasso: a long wire thread integrated in the proximal ends of the wire mesh that hangs freely in the stent lumen. Pulling it enables gradual removal of the stent inside-out. A secondary aim was success of stricture resolution.
Non-randomized, prospective follow-up study with 3 sequential cohorts of 8 patients with BBS.
Academic tertiary referral center.
Eligible patients had strictures either postsurgical (post-cholecystectomy (LCx) or liver transplantation (OLT)), due to chronic pancreatitis (CP), or papillary stenosis (PF). Strictures had to be located at least 2 cm below the liver hilum. All patients had one plastic stent in situ across the stricture and had not undergone previous treatment with either multiple plastic stents or fcSEMS.
The first cohort of patients underwent stent placement for 2 months, followed by 3 months if the stricture had not resolved. The second and third cohort started with 3 months and 4 months, respectively, both followed by another 4 months if indicated. Treatment success was defined by stricture resolution at cholangiography, the ability to pass an inflated extraction balloon and clinical follow-up (at least 6 months).
safety of stent removal. Secondary outcomes were complications and successful stricture resolution.
A total of 23 patients (11 female; 20-67 yrs) were eligible for final analysis. One patient developed a malignant neuroendocrine tumor in the setting of CP. Strictures were caused by CP (13), OLT (6), LCx (3) and PF (1). In total 39 fcSEMS were placed and removed. Removals were easy and without complications. Transient pain after insertion was common (13 of 23/56%) but was easily managed by analgesics in all patients. Other complications were cholecystitis (1), cholangitis due to stent migration (1, stent replaced) or stent clogging (2, managed endoscopically) and worsening of CP (2). In these patients, the fcSEMS was removed and replaced after pancreatic sphincterotomy and PD stent placement. Median follow-up was 15 months (range 11-25). Overall treatment success was 61% (14/23); in the CP group 46%, in the remaining patients 80% (p = 0.11). Patients with stricture resolution after removal of the first stent (n = 7; success 6/7) showed a trent towards a more sustained treatment success than patients who needed a 2nd stent placement (n = 16; success 8/16); p = 0.12).
Small number of patients with regard to secondary outcomes.
Removal of a new type of fcSEMS with a proximal retrieval lasso in patients with BBS proved easy and uncomplicated. Treatment success for CP strictures was higher compared to what is known from results of progressive plastic stenting protocols. For other indications treatment success was comparable to progressive plastic stenting, but with the prospect of fewer ERCP procedures.
Gastrointestinal endoscopy 02/2012; 75(4):783-9. · 6.71 Impact Factor
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ABSTRACT: We have developed a method to longitudinally classify subjects into two or more prognostic groups using longitudinally observed values of markers related to the prognosis. We assume the availability of a training data set where the subjects' allocation into the prognostic group is known. The proposed method proceeds in two steps as described earlier in the literature. First, multivariate linear mixed models are fitted in each prognostic group from the training data set to model the dependence of markers on time and on possibly other covariates. Second, fitted mixed models are used to develop a discrimination rule for future subjects. Our method improves upon existing approaches by relaxing the normality assumption of random effects in the underlying mixed models. Namely, we assume a heteroscedastic multivariate normal mixture for random effects. Inference is performed in the Bayesian framework using the Markov chain Monte Carlo methodology. Software has been written for the proposed method and it is freely available. The methodology is applied to data from the Dutch Primary Biliary Cirrhosis Study.
Statistics in Medicine 12/2010; 29(30):3267-83. · 1.88 Impact Factor
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ABSTRACT: The reported incidence of hepatocellular carcinoma (HCC) among patients with primary biliary cirrhosis (PBC) varies from 0.7-3.8%, whereas in cirrhotic patients the risk is considerably higher. Age, male sex, cirrhosis, and portal hypertension are reported risk factors. It has been suggested that ursodeoxycholic acid (UDCA) may protect against HCC. We aimed to define risk factors for the development of HCC at the time of PBC diagnosis and to identify, among patients treated with UDCA for a long term, a subgroup that could benefit from screening.
Prospective multicenter cohort study of patients with established PBC treated with 13-15 mg/kg/day UDCA. Age, sex, antimitochondrial antibodies, bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, aspartate amino transferase, cirrhosis, portal hypertension, Mayo Risk Score, prognostic class (based on bilirubin and albumin levels), and response to UDCA (normalization of bilirubin and/or albumin levels) were analyzed as potential risk factors in Cox regression analysis.
Three hundred and seventy-five patients were included, median follow-up was 9.7 years. HCC occurred in nine patients, corresponding with an annual incidence of 0.2%. The factor significantly associated with the development of HCC was the response to UDCA (P<0.001). The risk for HCC was highest in the group of nonresponders to UDCA: the 10 years incidence of HCC was 9% and the 15 years incidence was 20%. The number needed to screen in this subgroup was 11.
In UDCA treated PBC patients the risk of HCC is relatively low. The main risk factor for HCC in this study was the absence of biochemical response to UDCA after 1-year treatment.
European journal of gastroenterology & hepatology 12/2010; 22(12):1495-502. · 1.66 Impact Factor
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ABSTRACT: Colesevelam is an anion-exchange resin with a 7-fold higher bile acid-binding capacity and fewer side effects than cholestyramine, the current first-line treatment option for cholestatic pruritus. The aim of this trial was to compare the effects of colesevelam and a placebo in patients with cholestatic pruritus. In a randomized, double-blind, investigator-initiated, multicenter trial, patients with cholestatic pruritus, both treatment-naive and previously treated, received 1875 mg of colesevelam or an identical placebo twice daily for 3 weeks. The effect on pruritus was assessed with daily visual analogue scales, quality-of-life scores, and evaluations of cutaneous scratch lesions. The predefined primary endpoint was the proportion of patients with at least a 40% reduction in pruritus visual analogue scale scores. Thirty-eight patients were included, and 35 were evaluable: 17 took colesevelam, 18 took the placebo, 22 were female, 8 were treatment-naive, 14 had primary biliary cirrhosis, and 14 had primary sclerosing cholangitis. The mean serum bile acid levels were comparable between the groups before treatment (P = 0.74), but they were significantly different after treatment (P = 0.01) in favor of patients treated with colesevelam. Thirty-six percent of patients in the colesevelam group reached the primary endpoint versus 35% in the placebo group (P = 1.0). There were no significant differences between the groups with respect to pruritus scores, quality-of-life scores, and severity of cutaneous scratch lesions. Mild side effects occurred in one colesevelam-treated patient and four placebo-treated patients. CONCLUSION: Although colesevelam significantly decreased serum bile acid levels, this trial was unable to demonstrate that it was more effective than a placebo in alleviating the severity of pruritus of cholestasis.
Hepatology 10/2010; 52(4):1334-40. · 11.66 Impact Factor
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ABSTRACT: Retrograde double balloon enteroscopy (DBE) is important for evaluating the distal small bowel, but it is more challenging compared to the oral route. Optimizing small bowel insertion may enhance the diagnostic utility of the examination. We sought to determine if insertion depths achieved with retrograde DBE when performed as an isolated procedure differed significantly from when performed immediately following anterograde DBE.
A retrospective analysis was conducted of all retrograde DBE procedures performed at our center with comparisons made between "distal-only" DBE without preceding anterograde DBE and "combined" DBE after a prior same-day anterograde DBE.
Two hundred ninety retrograde DBE procedures were performed in 264 patients over 5 years. Success of terminal ileal intubation exceeded 95%. The mean insertion depth into the distal small bowel differed significantly with 112 cm (95% CI 95-129) in the "distal-only" group and 92 cm (95% CI 85-98) in the "combined" group (p = 0.01), with a trend toward a corresponding increased diagnostic yield of 48% versus 37%, respectively (p = 0.15). Multivariate regression analysis identified both insertion route strategy (distal-only > combined; p = 0.01) and type of DBE endoscope (diagnostic > therapeutic; p = 0.02) as significant predictors of retrograde insertion depth.
The insertion depth of retrograde DBE is significantly greater when carried out as a separate distal procedure and not in combination with a preceding anterograde DBE, and when performed using a diagnostic as opposed to the therapeutic DBE endoscope. This increased retrograde depth of insertion may be associated with an increased diagnostic yield.
Scandinavian journal of gastroenterology 10/2010; 46(2):220-6. · 2.08 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the diagnostic and therapeutic outcome of a primary balloon-assisted enteroscopy (BAE) approach in obscure gastrointestinal bleeding (OGIB) patients.
In the diagnostic approach of OGIB, both wireless capsule endoscopy (WCE) and BAE are used. The advantage of the primary wireless capsule endoscopy approach is its noninvasiveness. The main advantage of the primary BAE approach is the excellent diagnostic accuracy and the possibility to perform treatment during the same procedure.
A retrospective analysis of our BAE database with patients evaluated for OGIB was performed. BAE data, findings, and follow-up were obtained and evaluated.
One hundred and thirty-two patients (81 male, mean age 62 (11-88) years) were included. In 60 (45%) patients with follow-up, a likely cause for OGIB was found in the small bowel during BAE: angiodysplasia or vascular malformations in 42 (70%), ulcerative lesions in 7 (12%), tumors in 3 (5%), and other findings in 8 (13%) patients. Follow-up was available in 118 (89%) patients; mean time of follow-up was 18 (1-47) months. Thirty-eight (76%) patients with findings at BAE received endoscopic treatment, 27 (71%) of them improved, but anemia also improved spontaneously in 34 patients (63%) with normal findings during BAE. The total number of angiodysplasia per patient was not related to the outcome after treatment.
The primary BAE approach in OGIB patients has an acceptable diagnostic yield. Therapy seems successful at mid-term follow-up. A high frequency of spontaneous resolution of anemia in patients with normal findings during BAE was observed.
Journal of clinical gastroenterology 10/2010; 44(9):e195-200. · 2.21 Impact Factor
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Andreas E Kremer,
Job J W W Martens,
Wim Kulik,
Franziska Ruëff,
Edith M M Kuiper, Henk R van Buuren,
Karel J van Erpecum,
Jurate Kondrackiene,
Jesus Prieto,
Christian Rust,
Victoria L Geenes,
Catherine Williamson,
Wouter H Moolenaar,
Ulrich Beuers,
Ronald P J Oude Elferink
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ABSTRACT: Pruritus is a common and disabling symptom in cholestatic disorders. However, its causes remain unknown. We hypothesized that potential pruritogens accumulate in the circulation of cholestatic patients and activate sensory neurons.
Cytosolic free calcium ([Ca(2+)](i)) was measured in neuronal cell lines by ratiometric fluorometry upon exposure to serum samples from pruritic patients with intrahepatic cholestasis of pregnancy (ICP), primary biliary cirrhosis (PBC), other cholestatic disorders, and pregnant, healthy, and nonpruritic disease controls. Putative [Ca(2+)](i)-inducing factors in pruritic serum were explored by analytical techniques, including quantification by high-performance liquid chromatography/mass spectroscopy. In mice, scratch activity after intradermal pruritogen injection was quantified using a magnetic device.
Transient increases in neuronal [Ca(2+)](i) induced by pruritic PBC and ICP sera were higher than corresponding controls. Lysophosphatidic acid (LPA) could be identified as a major [Ca(2+)](i) agonist in pruritic sera, and LPA concentrations were increased in cholestatic patients with pruritus. LPA injected intradermally into mice induced scratch responses. Autotaxin, the serum enzyme converting lysophosphatidylcholine into LPA, was markedly increased in patients with ICP versus pregnant controls (P < .0001) and cholestatic patients with versus without pruritus (P < .0001). Autotaxin activity correlated with intensity of pruritus (P < .0001), which was not the case for serum bile salts, histamine, tryptase, substance P, or mu-opioids. In patients with PBC who underwent temporary nasobiliary drainage, both itch intensity and autotaxin activity markedly decreased during drainage and returned to preexistent levels after drain removal.
We suggest that LPA and autotaxin play a critical role in cholestatic pruritus and may serve as potential targets for future therapeutic interventions.
Gastroenterology 09/2010; 139(3):1008-18, 1018.e1. · 11.68 Impact Factor
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ABSTRACT: Gastrointestinal endoscopy databases are important for surveillance, epidemiology, quality control and research. A good quality of automatically generated databases to enable drawing justified conclusions based on the data is of key importance. The aim of this study is to validate the correctness of coding of a national automatically generated anonymous endoscopy database.
We evaluated a total of 500 colonoscopies performed in five larger hospitals of the TRANS.IT project focusing on endoscopy reporting. Randomly 500 examinations were selected from a total of 5,000 examinations and their generated endoscopic terminology codes as well as complete reports were analysed. Indications for the examination and described findings were scored for correctness and clinical relevance of the coding that would be exported to the anonymous database.
Indications were correctly coded in 92% of all examinations (range 76-100%) per hospital. Correct coding of findings ranged from 42% to 93% per hospital (mean 77%). Different correct coding proportions were seen varying with the diagnosis, with the highest correct coding rates in polyps, carcinoma and diverticular disease. Incorrect coded examinations were scored for clinical relevance. Overall 11% of the investigated examinations were incorrectly coded with clinical relevance.
Accuracy of clinically relevant endoscopy data recorded in the TRANS.IT anonymous central database is high. Further improvement is desirable, which may be achieved by education of individual endoscopists and enhancement of the program.
Scandinavian journal of gastroenterology 09/2010; 45(9):1121-6. · 2.08 Impact Factor
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ABSTRACT: A decrease in the need for liver transplantations (LTX) in Primary Biliary Cirrhosis (PBC), possibly related to treatment with ursodeoxycholic acid (UDCA), has been reported in the USA and UK. The aim of this study was to assess LTX requirements in PBC over the past 20 years in the Netherlands.
Analysis of PBC transplant data of the Dutch Organ Transplant Registry during the period 1988-2008, including both absolute and proportional numbers. The indication for LTX was categorized as liver failure, hepatocellular carcinoma or poor quality of life (severe fatigue or pruritus). Data were analysed for two decades: 1.1.1988-31.12.1997 (1(st)) and 1.1.1998-31.12.2007 (2(nd)). The severity of disease was quantified using MELD scores. To fit lines which show trends over time we applied a linear regression model.
A total of 110 patients (87% women) was placed on the waiting list. 105 patients were transplanted (1(st): 61, 2(nd): 44), 5 (5%) died while listed. The absolute annual number of LTX for PBC slightly decreased during the 20 year period, the proportional number decreased significantly. At the time of LTX the mean age was 53.6 yrs. (1(st): 53.4, 2(nd): 53.8), the mean MELD score 13.9 (1(st):14.5, 2(nd):13.0). The median interval from diagnosis to LTX was 90.5 months (1(st):86.5, 2(nd): 93.5). 69% of patients was treated with UDCA (1(st) 38%, 2(nd) 82%).
Over the past 20 years the absolute number of LTX for PBC in the Netherlands showed a tendency to decrease whereas the proportional decrease was significant. There was a trend over time toward earlier transplantation.
BMC Gastroenterology 01/2010; 10:144. · 2.42 Impact Factor
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ABSTRACT: In the Netherlands there are probably several thousands of patients with primary biliary cirrhosis (PBC), a slowly progressive liver disease mainly affecting middle-aged women. PBC has characteristics of an autoimmune disease but its precise aetiology remains unknown. Fatigue and pruritus are the main symptoms but patients may also be asymptomatic. The diagnosis can be established through the presence of cholestatic liver test abnormalities, antimitochondrial antibodies and diagnostic or compatible findings upon liver biopsy. Currently most patients are diagnosed with early disease. When treated with ursodeoxycholic acid these patients have a normal prognosis.
Nederlands tijdschrift voor geneeskunde 01/2009; 153:A483.
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ABSTRACT: Transcatheter local thrombolytic therapy in patients with acute, extended splanchnic venous thrombosis is controversial. Here we present our single-center experience with transcatheter thrombolytic therapy in these patients. All consecutive patients (n = 12) with acute, extended splanchnic venous thrombosis who underwent transcatheter thrombolytic therapy in our hospital, were included in this study. Thrombolytic therapy was successful for three thrombotic events and partially successful for four thrombotic events. Two patients developed minor procedure-related bleeding (17%). Six patients (50%) developed major procedure-related bleeding, with a fatal outcome in two. Transcatheter thrombolytic therapy in patients with acute, extended splanchnic vein thrombosis is found to be associated with a high rate of procedure-related bleeding. Therefore, thrombolysis should be reserved for patients in whom the venous flow cannot be restored by using conventional anticoagulant therapy or stent placement across the thrombosed vessel segment.
Thrombosis and Haemostasis 01/2009; 100(6):1084-8. · 5.04 Impact Factor
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ABSTRACT: Ursodeoxycholic acid (UDCA) improves laboratory liver test results in patients with primary biliary cirrhosis (PBC). Few studies have assessed the prognostic significance of biochemical data collected following UDCA treatment. We performed a prospective multicenter study of patients with PBC treated with UDCA to compare prognosis with biochemical response.
PBC was classified as early (pretreatment bilirubin and albumin levels normal), moderately advanced (one level abnormal), or advanced (both levels abnormal). Biochemical response was defined as proposed by Pares (decrease in alkaline phosphatase [ALP] level>40% of baseline level or normal level), Corpechot (ALP level<3-fold the upper limit of normal [ULN], aspartate aminotransferase level<2-fold the ULN, bilirubin level<1-fold the ULN), and our group (Rotterdam; normalization of abnormal bilirubin and/or albumin levels).
The study included 375 patients, and median follow-up time was 9.7 (range, 1.0-17.3) years. The prognosis for early PBC was comparable with that of the Dutch population and better than predicted by the Mayo risk score. Survival of responders was better than that of nonresponders, according to Corpechot and Rotterdam criteria (P<.001). Prognosis of early PBC was comparable for responders and nonresponders; prognosis of responders was significantly better in those with (moderately) advanced disease.
Prognosis for UDCA-treated patients with early PBC is comparable to that of the general population. Survival of those with advanced PBC with biochemical response to UDCA is significantly better than for nonresponders. Thus, UDCA may be of benefit irrespective of the stage of disease. Prognostic information, based on bilirubin and albumin levels, is superior to that provided by ALP levels.
Gastroenterology 01/2009; 136(4):1281-7. · 11.68 Impact Factor
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ABSTRACT: Primary sclerosing cholangitis (PSC) patients are at risk for developing cholangiocarcinoma (CCA) and colorectal carcinoma (CRC). Our aim was to assess the risk of malignancies and their influence on survival.
Data from PSC patients diagnosed between 1980 and 2006 in two university hospitals were retrieved. The Kaplan-Meier method and a time-dependent Cox regression model were used to calculate risks of malignancies and their influence on survival.
Two hundred and eleven patients were included, 143 (68%) were male and 126 (60%) had inflammatory bowel disease (IBD). Median transplantation-free survival was 14 years. The risk of CCA after 10 and 20 years was 9% and 9%, respectively. In patients with concomitant IBD the 10-year and 20-year risks for CRC were 14% and 31%, which was significantly higher than for patients without IBD (2% and 2% (P=0.008)). CCA, cholangitis, and age at entry were independent risk factors for the combined endpoint death or liver transplantation. Risk factors for the endpoint death were CCA, CRC, age, and symptomatic presentation.
Patients with PSC and IBD have a high long-term risk of developing CRC and this risk is about threefold higher than the risk for CCA. Both malignancies are associated with decreased survival.
Journal of Hepatology 11/2008; 50(1):158-64. · 9.26 Impact Factor
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ABSTRACT: Esophagogastric variceal bleeding is the most important complication of extrahepatic portal vein thrombosis (EPVT) and is usually treated endoscopically. Little is known about the prognosis of these patients.
To investigate the long-term clinical outcome and efficacy of endoscopic treatment in patients with esophagogastric variceal bleeding secondary to EPVT.
Retrospective observational study.
Single university center.
Twenty-seven consecutive patients with esophagogastric variceal bleeding, secondary to noncirrhotic, nonmalignant EPVT, who underwent endoscopic treatment between 1982 and 2005.
Endoscopic band ligation and/or endoscopic sclerotherapy.
The overall rebleeding risk, overall survival, complications of the endoscopic procedures, and predictive values of rebleeding. Analyses were performed by the Kaplan-Meier method and univariate Cox regression.
All patients were followed-up after the first endoscopically treated variceal bleeding. A total of 241 endoscopic procedures were performed. In all patients, initial control of bleeding was obtained. The overall rebleeding risk was 23% (95% CI, 0%-24%) at 1 year and 37% (95% CI, 43%-83%) at 5 years. Extension of thrombosis into the splenic vein and the presence of fundal varices were significant predictors of rebleeding, with a nearly 5-fold increased risk for patients with EPVT and fundal varices at the time of the first variceal hemorrhage (hazard ratio 5.07, P = .01). A portosystemic shunt procedure was performed in 5 patients: 4 for variceal bleeding and in one patient for refractory ascites. Seven patients died, none from variceal bleeding. Overall 5-year and 10-year survivals were 100% and 62% (95% CI, 38%-96%), respectively.
Retrospective design.
In patients with variceal bleeding secondary to EPVT endoscopic treatment, in particular, band ligation appears safe and effective. EPVT-related mortality is primarily determined by other causes than variceal bleeding.
Gastrointestinal Endoscopy 06/2008; 67(6):821-7. · 4.88 Impact Factor
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ABSTRACT: The clinical outcome of a covered vs. uncovered transjugular intrahepatic portosystemic shunt (TIPS) for patients with Budd-Chiari syndrome (BCS) is as yet largely unknown.
To compare patency rates of bare and polytetrafluoroethylene (PTFE)-covered stents, and to investigate clinical outcome using four prognostic indices [Child-Pugh score, Rotterdam BCS index, modified Clichy score and Model for End-Stage Liver Disease (MELD)].
Consecutive patients with BCS who had undergone TIPS between January 1994 and March 2006 were evaluated in a retrospective review in a single centre.
Twenty-three TIPS procedures were performed on 16 patients. The primary patency rate at 2 years was 12% using bare and 56% using covered stents (P=0.09). We found marked clinical improvement at 3 months post-TIPS as determined by a drop in median Child-Pugh score (10-7, P=0.04), Rotterdam BCS index (1.90-0.83, P=0.02) and modified Clichy score (7.77-2.94, P=0.003), but not in MELD (18.91-17.42, P=0.9). Survival at 1 and 3 years post-TIPS was 80% (95% CI: 59-100%) and 72% (95% CI: 48-96%). Four patients (25%) died and one required liver transplantation.
A transjugular intrahepatic portosystemic shunt using PTFE-covered stents shows better patency rates than bare stents in BCS. Moreover, TIPS leads to an improvement in important prognostic indicators for the survival of patients with BCS.
Liver international: official journal of the International Association for the Study of the Liver 03/2008; 28(2):249-56. · 3.82 Impact Factor
