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Contains fulltext : 215386.pdf (Publisher’s version ) (Open Access) BACKGROUND: Autoimmune hepatitis requires long-term therapy, and systemic corticosteroids are the backbone of therapeutic management. Prolonged use of corticosteroids may lead to adverse events but data from long-term studies are mainly derived from studies in rheumatic diseases. AIM: To assess cataract, diabetes and fractures in relation to corticosteroid doses in the long-term maintenance treatment of patients with autoimmune hepatitis. METHODS: We retrospectively collected data on 476 patients (77% women) with an established diagnosis of autoimmune hepatitis. Binary logistic regression with a generalised estimating equation was used to analyse the association between current corticosteroid use and the incidence of cataract, diabetes and fractures with onset after autoimmune hepatitis diagnosis. We corrected for sex, age, cirrhosis at diagnosis and predniso(lo)ne use in the prior 3 years to account for possible ongoing effects. RESULTS: A total of 6634 years, with a median of 13 (range 1-40) per patient were recorded. The median age at diagnosis was 44 years (range 2-88). Adverse events were documented in 120 (25%) patients. Low-dose predniso(lo)ne (0.1-5.0 mg/d) increased the odds of fractures whereas higher doses (>5.0 mg/d) increased the odds of cataracts and diabetes. Budesonide increased the odds of cataract and fractures; this effect was independent of predniso(lo)ne use in the prior 1, 2 or 3 years. CONCLUSIONS: Even low doses of corticosteroids frequently lead to substantial adverse events refuting the assumption that adverse events are prevented by administering low doses.

Introduction & Aims: Small studies have found that black patients with autoimmune hepatitis (AIH) present with more aggressive disease. We aimed to characterize the presentation and outcome in black and white patients with AIH. Methods: We performed a retrospective study, collecting information from databases of patients with AIH attending the Institute of Liver studies at King's College Hospital, London (1971–October 2015, the Royal Free Hospital, London (1982 through December 2016) and the multicenter Dutch Autoimmune Hepatitis Study Group cohort (2006–August 2016). We identified 88 black patients with AIH and we compared their clinical characteristics and outcomes to 897 white patients with AIH. Results: Black patients presented at a younger age (median 38 years vs 45 years) (P =.007), had higher IgG levels (mean 31.0 mg/dL vs 27.5 mg/dL) (P =.04), but there were no significant differences between groups in auto-antibody profiles, International AIH Group scores, or sex distribution of disease. A higher proportion of black patients had systemic lupus erythematosus (10%) than white patients (2%) (P ≤.001). There was no significant difference in proportions of patients with a response to standard therapy (86% for black patients vs 91% for white patients; P =.20) or in rate of relapse (57% vs 50%; P =.3). Despite this, black patients had an increased risk of liver transplantation and liver-related death (hazard ratio 2.4, 95% confidence interval, 1.4–4.0; P

Autoimmune pancreatitis (AIP) is often difficult to distinguish from pancreatic carcinoma or other pancreatobiliary diseases. High serum levels of carbohydrate antigen 19-9 (Ca 19-9) are indicative of malignancies, whereas high levels of immunoglobulin (Ig)G4 (> 1.4 g/l) are characteristic of AIP. We investigated whether serum levels of these proteins can differentiate between these diseases. We measured levels of Ca 19-9 and IgG4 in serum samples from 33 patients with AIP, 53 with pancreatic carcinoma, and 145 with other pancreatobiliary disorders. We determined cut-off levels for each assay. Logistic regression analysis was used to evaluate combined data on Ca 19-9, IgG4, and bilirubin levels. Low levels of Ca 19-9 were independently associated with AIP, compared with pancreatic adenocarcinoma [odds ratio (OR) 0.28; 95 % confidence interval (CI) 0.13-0.59; p = 0.0001]. Using an upper level of 74 U/ml, the assay for Ca 19-9 identified patients with AIP with 73 % sensitivity and 74 % specificity. Using a lower level of 2.6 g/l, the assay for IgG4 identified these patients with 70 % sensitivity and 100 % specificity. Combining data, levels of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l identified patients with AIP with 94 % sensitivity and 100 % specificity. Patients with AIP have lower levels of Ca 19-9 than those patients with pancreatic carcinoma. Measurement of either the Ca 19-9 or the IgG4 level alone are not accurate enough for diagnosis. However, the combination of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l distinguishes patients with AIP from those patients with pancreatic carcinoma with 94 % sensitivity and 100 % specificity.

Item does not contain fulltext Abstract Background and aims. Epidemiological data on autoimmune hepatitis (AIH) are scarce. In this study, we determined the clinical and epidemiological characteristics of AIH patients in the Netherlands (16.7 million inhabitants). Methods. Clinical characteristics were collected from 1313 AIH patients (78% females) from 31 centers, including all eight academic centers in the Netherlands. Additional data on ethnicity, family history and symptoms were obtained by the use of a questionnaire. Results. The prevalence of AIH was 18.3 (95% confidential interval [CI]: 17.3-19.4) per 100,000 with an annual incidence of 1.1 (95% CI: 0.5-2) in adults. An incidence peak was found in middle-aged women. At diagnosis, 56% of patients had fibrosis and 12% cirrhosis in liver biopsy. Overall, 1% of patients developed HCC and 3% of patients underwent liver transplantation. Overlap with primary biliary cirrhosis and primary sclerosing cholangitis was found in 9% and 6%, respectively. The clinical course did not differ between Caucasian and non-Caucasian patients. Other autoimmune diseases were found in 26% of patients. Half of the patients reported persistent AIH-related symptoms despite treatment with a median treatment period of 8 years (range 1-44 years). Familial occurrence was reported in three cases. Conclusion. This is the largest epidemiological study of AIH in a geographically defined region and demonstrates that the prevalence of AIH in the Netherlands is uncommon. Although familial occurrence of AIH is extremely rare, our twin data may point towards a genetic predisposition. The high percentage of patients with cirrhosis or fibrosis at diagnosis urges the need of more awareness for AIH.

The use of self-expandable metal stents (SEMS) has occasionally been described for the treatment of uncontrollable esophageal variceal bleeding (EVB) as a bridge to an alternative treatment option (i. e. transjugular intrahepatic portosystemic shunt [TIPS]). It is currently not known whether SEMS placement is appropriate for more than temporary hemostasis. This case series report describes five patients in whom EVB could not be controlled with variceal band ligation and who were not suitable to undergo a TIPS procedure at the time of bleeding. SEMS were placed in these patients with the intent of definitive treatment. Successful initial hemostasis was achieved in all five patients, and sustained hemostasis occurred in four. Stents were removed from two patients after > 14 days and remained in situ until death in three other patients (range 6 - 214 days). No complications related to this longer duration were observed. In one case, TIPS could be performed at a later stage. SEMS could be a definitive treatment for uncontrollable esophageal bleeding in patients with a limited life expectancy or those unsuitable for TIPS at the time of bleeding.

Occasionally patients undergoing resection for presumed malignancy of the pancreatic head are diagnosed postoperatively with benign disease. Autoimmune pancreatitis (AIP) is a rare disease that mimics pancreatic cancer. We aimed to determine the prevalence of benign disease and AIP in patients who underwent pancreatoduodenectomy (PD) over a 9-year period, and to explore if and how surgery could have been avoided.All patients undergoing PD between 2000 and 2009 in a tertiary referral centre were analyzed retrospectively. In cancer-negative cases, postoperative diagnosis was reassessed. Preoperative index of suspicion of malignancy was scored as non-specific, suggestive, or high. In AIP patients, diagnostic criteria systems were checked.A total of 274 PDs were performed for presumed malignancy. The prevalence of benign disease was 8.4 %, overall prevalence of AIP was 2.6 %. Based on preoperative index of suspicion of malignancy, surgery could have been avoided in 3 non-AIP patients. All AIP patients had sufficient index to justify surgery. If diagnostic criteria would have been checked; however, surgery could have been avoided in one to five AIP patients.The prevalence of benign disease in patients who underwent PD for presumed malignancy was 8.4 %, nearly one-third attributable to AIP. Although misdiagnosis of AIP as carcinoma is a problem of limited quantitative importance, every effort to establish the correct diagnosis should be undertaken considering the major therapeutic consequences. IgG4 measurement and systematic use of diagnostic criteria systems are recommended for every candidate patient for PD when there is no histological proof of malignancy.

Background Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment. Aim To assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes. Methods Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression. Results Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P < 0.001). Conclusions Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine-intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often effective.

Background and aims: Ursodeoxycholic acid (UDCA) has an established effect on liver bio-chemistries in primary biliary cirrhosis (PBC). Few studies have evaluated long-term laboratory treatment effects and data beyond 6 years are not available. The aim of this study was to assess the long-term evolution of liver biochemistries during prolonged treatment with UDCA in biochemically non-advanced PBC. Patients and methods: Prospective multicenter cohort study of patients with PBC with pretreatment normal bilirubin and albumin, treated with UDCA 13-15 mg/kg/day. At yearly intervals, follow-up data including serum bilirubin, alkaline phosphatase (ALP), transaminases, albumin and IgM were collected. Data were analyzed with a repeated measurement model. Results: Two hundred and twenty-five patients were included and followed during a median period of 10.3 years. Following 1-year treatment with UDCA 36-100% of the total biochemical improvement was achieved, the maximum response was observed after 3 years. After initial improvements, bilirubin and AST levels increased and albumin levels significantly decreased after 6-10 years. However, these changes were of limited magnitude. The beneficial effects on ALT and ALP were maintained while IgM continued to decrease. Conclusion: In non-advanced PBC the biochemical response to UDCA is maintained up to 15 years. The long-term evolution of bilirubin, albumin and ALT differs from that of ALP and AST. The mean IgM level normalised and levels continued to decrease during the period of follow-up. (C) 2010 Elsevier Masson SAS. All rights reserved.

It is estimated that 10–30% of patients with Crohn’s disease (CD) have small bowel (SB) involvement, but the exact frequency and clinical relevance of these findings is unknown. Double-balloon enteroscopy (DBE) enables endoscopic visualization of the SB. In this study we evaluated whether DBE is a feasible technique for detection of CD localized in the SB in CD patients with clinical suspicion of SB lesions and whether these findings have clinical impact. Retrospectively we analyzed 52 DBE procedures in 40 CD patients (16 males, mean age 40 years, mean duration of CD 15 years). Included patients had clinical suspicion of small bowel CD activity, including persistent abdominal discomfort (n = 27), iron deficiency anemia (n = 9) and/or hypomagnesemia (n = 4). Active small bowel CD was found in 24 (60%) patients, leading to a change in therapy in 18 patients (75%). After a mean follow-up of 13 months, 15 (83%) had persistent clinical improvement with a significant drop of mean CDAI from 178 to 90, after a mean follow-up of 13 months. DBE is a useful diagnostic tool for the evaluation of SB lesions in CD patients. The significance of these findings is emphasized by the fact that adjustment of therapy in the majority of these patients leads to significant and sustained clinical improvement.

SummaryBackground Pruritus is a common symptom associated with cholestatic liver diseases. To date only small single centre case series have suggested efficacy of nasobiliary drainage in relieving cholestatic pruritus. Aim To perform a multicentre study to evaluate the safety and efficacy of nasobiliary drainage in cholestatic pruritus. Methods This was a retrospective study of all patients treated with nasobiliary drainage for refractory cholestatic pruritus between 2006 and 2015 at five European centres. Pruritus was quantified using a visual analogue scale (VAS) and liver enzymes, serum bilirubin and total serum bile salts (TBS) were measured before (pre-NBD) and after nasobiliary drainage (post-NBD). We analysed the duration of treatment response and associated complications. Results In total, 27 patients (59% females) underwent 29 nasobiliary drainage procedures. The median duration of NBD was 7 days. NBD decreased pruritus in 89.6% of cases (VAS from 10.0 to 0.3, P < 0.0001). The median percentage decline in pruritus VAS was 94% and 33% of patients were free of pruritus within 24 h of starting drainage. The duration of treatment response was independent of duration of drainage (P = 0.12) and bile output. Significant improvements were seen in the median levels of serum alkaline phosphatase (P = 0.001) and serum bilirubin (P = 0.03) but not in serum TBS (P = 0.07). Mild post-endoscopic retrograde cholangiopancreatography pancreatitis (31%) was the most frequent complication. Conclusions Nasobiliary drainage is effective in relieving cholestatic pruritus in most patients and has favourable effect on biomarkers of cholestasis. Nasobiliary drainage may be associated with high risk of adverse events, especially pancreatitis. Prospective studies are needed to confirm our findings.

SUMMARY Background Ascites is the most common complication of cirrhosis, associated with an expected survival below 50% after 5 years. Prognosis is particularly poor for patients with refractory ascites and for those developing complications, including spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). Aim To provide an evidence-based overview of the pathophysiology, diagnosis and clinical management of ascites secondary to liver cirrhosis. Methods Review based on relevant medical literature. Results Portal hypertension, splanchnic vasodilatation and renal sodium retention are fundamental in the pathophysiology of ascites formation. The SAAG (serum-ascites albumin gradient) allows reliable assessment of the cause of ascites. The majority of cirrhotic patients with ascites can be managed with dietary sodium restriction in combination with diuretic agents. Large volume paracentesis with albumin suppletion and TIPS are therapeutic options in patients with refractory ascites. Prophylactic antibiotics for SBP should be given in certain patient populations. Conclusions Recent advances in the diagnosis and treatment of ascites and associated complications have improved the medical management and poor prognosis of patients with these manifestations of advanced liver disease. Early diagnosis, adequate treatment and focus on prevention of complications remain essential as well as timely referral for liver transplantation.

Background Extrahepatic portal vein thrombosis is an important cause of non-cirrhotic portal hypertension. Aim To provide an update on recent advances in the aetiology and management of acute and chronic non-cirrhotic non-malignant extrahepatic portal vein thrombosis. Method A PubMed search was performed to identify relevant literature using search terms including 'portal vein thrombosis', 'variceal bleeding' and 'portal biliopathy'. Results Myeloproliferative disease is the most common risk factor in patients with non-cirrhotic non-malignant extrahepatic portal vein thrombosis. Anticoagulation therapy for at least 3 months is indicated in patients with acute extrahepatic portal vein thrombosis. However, in patients with extrahepatic portal vein thrombosis due to a prothrombotic disorder, permanent anticoagulation therapy can be considered. The most important complication of extrahepatic portal vein thrombosis is oesophagogastric variceal bleeding. Endoscopic treatment is the first-line treatment for variceal bleeding. In several of the patients with extrahepatic portal vein thrombosis biliopathy changes on endoscopic retrograde cholangiography (ERCP) have been reported. Dependent on the persistence of the biliary obstruction, treatment can vary from ERCP to hepaticojejunostomy. Conclusion Prothrombotic disorders are the major causes of non-cirrhotic, non-malignant extrahepatic portal vein thrombosis and anticoagulation therapy is warranted in these patients. The prognosis of patients with non-cirrhotic, non-malignant extrahepatic portal vein thrombosis is good, and is not determined by portal hypertension complications but mainly by the underlying cause of thrombosis.

BACKGROUND Since the introduction of TIPS (the transjugular intrahepatic portosystemic shunt) into clinical practice in 1989, substantial knowledge, partially derived from controlled trials, has become available regarding technical and clinical aspects of the procedure. A number of prospective studies have assessed the long-term patency of radiological shunts, the recognized main technical weakness of the procedure. METHODS Review of published data regarding the optimal indications and long-term patency of TIPS. RESULTS Information on the long-term patency of TIPS is surprisingly scarce. Within 2 years of TIPS creation, re-interventions to re-establish or maintain the patency of the shunt are required in 70%-90% of patients, and in 20%-40% total occlusion develops. Limited available data suggest, however, that in about 80% of patients the shunt is patent after 3-5 years. There is consensus that TIPS is a main, second-line treatment option for variceal haemorrhage not responding to other therapies. Although widely used for treating refractory ascites, gastric variceal bleeding and Budd-Chiari syndrome, these indications require more study. A number of other potential indications remain poorly defined. CONCLUSION TIPS is a major treatment modality to manage the complications of portal hypertension and Budd-Chiari syndrome. The available data indicate that TIPS is not only a short-term treatment option but may provide long-term portosystemic decompression. Technical improvements, e.g. the use of covered or drug-eluting stents, are essential to reduce the high rate of shunt dysfunction.

Direct percutaneous endoscopic jejunostomy (DPEJ) has emerged as a viable alternative for percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) in patients who cannot tolerate gastric feeding. Reportedly, DPEJ placement with regular endoscopes fails in up to one-third of cases. The aim of the current study was to assess the efficacy and safety of single-balloon enteroscopy (SBE)-assisted DPEJ. The DPEJ placement technique was comparable to conventional PEG placement. A total of 12 DPEJ procedures were performed in 11 patients (mean age 55 years [range 24 – 83 years]; seven males). SBE-assisted DPEJ was successful in 11 of the 12 procedures (92 %). Post-procedural complications included gastroparesis and aspiration pneumonia in one case each. We conclude that SBE-assisted DPEJ placement seems a safe and successful approach for patients requiring jejunal enteral feeding.

A 65-year-old man was referred for assessment of advanced liver disease. Seventeen years previously he had been diagnosed with ulcerative colitis, and 7 years later with primary sclerosing cholangitis (PSC). After several episodes with variceal bleeding caused by secondary biliary cirrhosis, a transjugular intrahepatic portosystemic shunt (TIPS) was created. Because of recurrent bacterial cholangitis, endoscopic retrograde cholangiography was performed, showing irregular narrowing of the intrahepatic bile ducts with saccular dilatations, findings considered compatible with PSC (figure 1). Also, a round filling defect in the common bile duct (CBD) was noted. After biliary sphincterotomy, a 6 mm polyp was removed. Histopathology review revealed a papillary adenoma with low-grade dysplasia. Figure 1 Cholangiography showing irregular intrahepatic bile ducts, saccular dilatations …

BACKGROUND AND STUDY AIMS: Direct endoscopic retrograde cholangiopancreatography (ERCP) has become the standard for establishing the diagnosis of primary sclerosing cholangitis (PSC), while endoscopic procedures play an increasingly important therapeutic role. However, many believe that this procedure carries a significant risk of infection and other complications. We assessed the incidence of complications within 1 week of ERCP in patients with PSC. PATIENTS AND METHODS: In a multicenter study, patients who underwent ERCP for (suspected) PSC were prospectively followed for the occurrence of complications after the procedure. RESULTS: A total of 106 ERCPs performed in 83 patients were evaluated. Complications occurred on ten occasions (9%): pancreatitis (n = 3), cholangitis (n = 2), increase of cholestasis (n = 2), postsphincterotomy bleeding (n = 1), cystic duct perforation (n = 1), and venous thrombosis (n = 1). All complications resolved quickly with proper therapy. Complications were more likely when ERCP was done to evaluate specific complaints such as jaundice or recurrent cholangitis (9/59) than after a purely diagnostic ERCP (1/47 relative risk [RR] 7.2, 95% confidence interval [CI] 1.00 to 153). Therapeutic interventions performed during ERCP (e.g. placement of endoprosthesis, dilation of strictures) also increased the risk of postprocedural complications (RR 4.5, 95 % CI 0.94 to 30). CONCLUSIONS: ERCP is a safe method for establishing the diagnosis of PSC in asymptomatic patients (2 % complication rate). Although ERCP in symptomatic patients carries a higher risk (14%), this can be justified by the benefits of endoscopic therapy.

OBJECTIVE PSC has characteristics of an (auto)immune-mediated disease: however, few studies have evaluated corticosteroid therapy for this disorder. METHODS We performed an 8-wk double-blind randomized pilot study to assess the effects of additional treatment with 9 mg budesonide (n = 6) versus 3 mg budesonide (n = 6) versus 10 mg prednisone (n = 6) in patients who had been treated with UDCA (mean dose, 12 mg/kg/day) for at least 5 months without achieving biochemical remission. Pruritus and fatigue were evaluated using visual analog scales. Serum liver biochemistry was measured every 4 wk. At entry and at the end of the trial, adrenocorticotrophic hormone (ACTH) and dehydroepiandrosterone (DHEA) were measured to assess effects on the pituitary-adrenal axis. Duodenal bile was collected for assessment of biliary corticosteroid activity. RESULTS Pruritus decreased significantly more in the prednisone group compared to both the 3-mg and the 9-mg budesonide groups (p < 0.05). Alkaline phosphatase (mean: -23.4%; p = 0.03) and IgG (mean: -16.2%; p = 0.04) decreased in the prednisone group, whereas bilirubin, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase did not change significantly. No significant clinical or liver biochemical changes were observed in the 3-mg and 9-mg budesonide groups. Significantly larger drops in serum ACTH were found in the 10-mg prednisone group (-40.7%; p = 0.04) and 9-mg budesonide group (-36.6%; p = 0.02) compared to the 3-mg budesonide group (+ 19.0%). No significant differences in percentage change in baseline values for DHEA between the three treatment arms were found. Mononuclear cell proliferation assays did not demonstrate corticosteroid activity in bile. Autoimmune hepatitis was observed in one case (9 mg budesonide) when corticosteroids were tapered off. CONCLUSION The results of this pilot study suggest only minor beneficial short-term effects of prednisone but not budesonide on symptoms and serum liver tests in UDCA-treated PSC patients.

Background: Ursodeoxycholic acid (UDCA) prolongs transplantation-free survival in primary biliary cirrhosis (PBC). However, the optimal therapeutic dose has not been established. Aim: To compare the effects of UDCA administered in daily doses of 10 vs. 20 mg/kg on symptoms, liver biochemistry and biliary UDCA enrichment. Methods: A 6-month multicentre randomized open controlled trial was conducted to assess the effects of an increase in the dose of UDCA to 20 mg/kg/day vs. continuation of 10 mg/kg/day for patients who had not achieved biochemical normalization during treatment for at least 6 months with the 10 mg/kg dose. Clinical and laboratory evaluations were performed at entry and at 3-month intervals. The percentage UDCA in duodenal bile was assessed at entry and at 6 months. Results: Sixty-one patients were enrolled. No side-effects of UDCA were observed. Within the 20 mg/kg/day group significant decreases were found for alkaline phosphatase (− 8%; P = 0.003), aspartate aminotransferase (− 11%; P = 0.01), alanine aminotransferase (− 17%; P

Item does not contain fulltext BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. METHODS: We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. RESULTS: We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 x 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 x 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 x 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 x 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 x 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. CONCLUSIONS: In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases.

Summary Background and aims It remains unclear when anticoagulant therapy should be given in patients with non-cirrhotic portal vein thrombosis (PVT). The 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. The overall thrombotic risk at 1, 5 and 10 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 (hazard ratio [HR] 0.2, P = 0.1), yet the only significant predictor of recurrent thrombotic events was the presence of a prothrombotic disorder (HR 3.1, P = 0.03). In 37 patients, 83 gastrointestinal bleeding events occurred. The re-bleeding risk at 1, 5 and 10 years was 19%, 46% and 49%, respectively. Anticoagulation therapy (HR 2.0, P ≤ 0.01) was a significant predictor of (re)bleeding. Anticoagulation therapy had no effect on the 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.

Is transjugular intrahepatic portosystemic shunt (TIPS) preferable to a surgical shunting procedure in patients who are expected to benefit from a portal-systemic shunt? Since randomized trials comparing these procedures have not yet been reported, we attempted to define the present best therapeutic strategy by reviewing both the recent literature on TIPS and surgical shunting and our first experience with TIPS. The results suggest that TIPS is just as effective as surgical shunting but is associated with a lower morbidity and mortality. Procedure related deaths seem rare. In our scries of 16 patients there was one death within 30 days. Seven early complications including stent dislodgement, early occlusion, encephalopathy and haemolysis were noted. The incidence of long-term complications, especially encephalopathy and shunt occlusion, seems comparable for both shunting procedures. Major advantages of TIPS are its therapeutic efficacy in patients with ascites and the fact that the technical difficulties ...

Introduction Hepatocellular carcinoma (HCC) is an important but infrequent outcome in primary biliary cirrhosis (PBC). Improved risk evaluation is an important goal for stratified surveillance. Methods Risk-factor analysis of the ‘Global PBC Study Group’ comprising 15 centres across North America and Europe spanning >40-years follow-up was performed using Cox proportional hazards model, logistic regression and Kaplan-Meier estimates (SPSSv21). Results Of 3546 patients with PBC (med. follow-up 8.6 yrs; IQR 4.4–14.1), 131 developed HCC. Excluding those who developed HCC within 12 months of PBC diagnosis (n = 23), median time to HCC was 12.7 yrs (6.9–16.8) and subsequent survival 1.1 yrs. (0.2–2.7). At diagnosis, factors associated with HCC development were male gender (adj. HR: 4.4;1.4–12.2, p = 0.014) and thrombocytopenia (adj. HR: 4.5;1.4–14.8, p = 0.012). Use of ursodeoxycholic acid per-se was not associated with future risk of HCC, but stratification of risk by biochemical response at 12 months was effective by Rotterdam (adj. HR: 8.9;2.1–37.3, P = 0.003), Paris-I (adj. HR: 7.6;2.0–29.0, p = 0.003) or Toronto criteria (HR: 5.6;1.6–18.8, P = 0.006). Five (4.6 vs. 0.2%) and 10-year (13%vs.1.9%) HCC incidence was significantly increased for biochemical non-responders (p = 2.2 × 10 –9 ), and by multivariate analysis non-response remained the only significant risk factor. Conclusion Our uniquely powered cohort allows robust demonstration that 12-month biochemical non-response is associated with an increased risk of developing HCC in PBC. Routine surveillance in those achieving biochemical response is unlikely cost-effective. Disclosure of Interest None Declared.

Contains fulltext : 79676.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with inflammatory bowel disease (IBD) and concurrent primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC) than IBD patients without PSC. The aim of this study was to investigate potential clinical differences between patients with CRC in IBD and those with CRC in IBD and PSC, as this may lead to improved knowledge of underlying pathophysiological mechanisms of CRC development. METHODS: The retrospective study from 1980-2006 involved 7 Dutch university medical centers. Clinical data were retrieved from cases identified using the national pathology database (PALGA). RESULTS: In total, 27 IBD-CRC patients with PSC (70% male) and 127 IBD-CRC patients without PSC (59% male) were included. CRC-related mortality was not different between groups (30% versus 19%, P = 0.32); however, survival for cases with PSC after diagnosing CRC was lower (5-year survival: 40% versus 75% P = 0.001). Right-sided tumors were more prevalent in the PSC group (67% versus 36%, P = 0.006); adjusted for age, sex, and extent of IBD, this difference remained significant (odds ratio: 4.8, 95% confidence interval [CI] 2.0-11.8). In addition, tumors in individuals with PSC were significantly more advanced. CONCLUSIONS: The right colon is the predilection site for development of colonic malignancies in patients with PSC and IBD. When such patients are diagnosed with cancer they tend to have more advanced tumors than patients with IBD without concurrent PSC, and the overall prognosis is worse. Furthermore, the higher frequency of right-sided tumors in patients with PSC suggests a different pathogenesis between patients with PSC and IBD and those with IBD alone.

were independent variables related to ATX activity. In terms of HRQoL, serum ATX was associated with fatigue (r = 0.218; p =0.02) in PBC-40 as well as fatigue (r = 0.217; p =0.02), cognitive (r = 0.207; p =0.03) and emotional (r = 0.202; p =0.03) domains of the PBC27 questionnaire. No correlations were found with generic SF-36 domains, except for physical functioning (r = 0.204; p =0.03). Conclusions: In patients with PBC, serum ATX is not only associated with pruritus but may also be involved in impairment of further aspects of patients’ quality of life and liver dysfunction. Thus, ATX inhibitors could be of potential benefit not only in the treatment of pruritus but also other incapacitating symptoms related to chronic cholestasis.

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are major causes of morbidity and a growing burden to the Austrian healthcare system. Contact points and specialized facilities are a fundamental basis for speedy diagnosis and fast appropriate treatment. The objective of our study was to assess the number of specialized facilities available for patients suffering from CD or UC and compare their number to the respective prevalence on a per-county level. Moreover, we compared the prevalenceadjusted numbers to the inflammatory rheumatic diseases to assess possible differences in quality of care. Methods: We conducted desk research on the epidemiological parameters of incidence and prevalence of both inflammatory diseases of the bowel (CD and CU) and inflammatory diseases of the bones and joints (rheumatic arthritis, RA; psoriatic arthritis, PsA; ankylosing spondylitis, AS) in Austria. We adjusted the data to exclude comorbidities and when necessary adjusted international data using data from the Austrian Central Statistics Office. To obtain comparable numbers for points of call catering to gastroenterologic and rheumatic patients respectively, we utilized and analyzed data from two novel applications for mobile phones aimed at Austrian patients (RHEUMA AKTIV and DARM AKTIV, respectively). Results: According to our calculations, there are 68,486 patients suffering from UC or CD in Austria. 69 points of call are listed in the DARM AKTIV application. Looking at these numbers in conjunction with the prevalence estimates, this leads to an Austrian average of 993 patients per point of call. However, there are huge disparities across the Austrian counties ranging from 514 patients per point of call in Carinthia to 1,641 patients per point of call in Upper Austria. Taking into account the three most common inflammatory rheumatic diseases RA, PsA and AS, we calculated the total number of Austrians affected to be 108,319. The disparities across the Austrian counties is even more pronounced for the rheumatic diseases and ranges from 764 patients per point of call in Salzburg to 6,922 patients per point of call in Lower Austria. Conclusions: Our study has brought new insights regarding the policy landscape for patients suffering from inflammatory diseases of the bowel or the bones and joints in Austria. We have identified huge disparities across the counties of Austria and conclude that quality of care and access to treatment may also differ across Austria. P658 Colorectal cancer in primary sclerosing cholangitis: the importance of surveillance K. Boonstra1 *, R. Weersma2, K.J. van Erpecum3, E. Rauws1, M. Spanier4, A. Poen5, K. van Nieuwkerk6, J. Drenth7, B. Witteman8, H. Tuynman9, A. Naber10, P. Kingma11, H. van Buuren12, B. van Hoek13, F. Vleggaar3, U. Beuers1, C. Ponsioen1. 1Academic Medical Center Amsterdam, Gastroenterology and Hepatology, Amsterdam, Netherlands, 2University Medical Center Groningen, Gastroenterology and Hepatology, Groningen, Netherlands, 3University Medical Center Utrecht, Gastroenterology and Hepatology, Utrecht, Netherlands, 4Rijnstate Hospital, Gastroenterology and Hepatology, Arnhem, Netherlands, 5Isala Clinics, Gastroenterology and Hepatology, Zwolle, Netherlands, 6VU Medical Center, Gastroenterology and Hepatology, Amsterdam, Netherlands, 7Radboud University Nijmegen Medical Center, Gastroenterology and Hepatology, Nijmegen, Netherlands, 8Gelderse Vallei Hospital, Gastroenterology and Hepatology, Ede, Netherlands, 9Medical Center Alkmaar, Gastroenterology and Hepatology, Alkmaar, Netherlands, 10Tergooiziekenhuizen, Gastroenterology and Hepatology, Hilversum, Netherlands, 11Tergooiziekenhuizen, Gastroenterology and Hepatology, Blaricum, Netherlands, 12Erasmus University Medical Center, Gastroenterology and Hepatology, Rotterdam, Netherlands, 13Leiden University Medical Center, Gastroenterology and Hepatology, Leiden, Netherlands

SIRS, Garcia-Buey and Moreno-Otero nicely summarise the literature on mycophenolate mofetil (MM) in autoimmune hepatitis (AIH) and overlap syndromes. The Dutch Autoimmune Hepatitis Group (DAHG) shows that second-line MM induces remission in 67% of patients with AIH and intolerance to azathioprine (AZA). In AIH and AZA nonresponse, remission was achieved with MMF in only 13%, and all deaths, liver transplantations and decompensations of cirrhosis occurred in this group. Therefore, in AIH and AZA-nonresponse other options, including liver transplantation, seem more appropriate. This is consistent with the findings of Hennes et al. For all patients with overlap syndromes, MM appears a valuable treatment option. In the DAHG cohort, MM induced remission in 63% and 57%, and response in 15% and 14% after AZA intolerance and nonresponse respectively. Recently, adding MM and budesonide appeared beneficial in primary biliary cirrhosis (PBC) with insufficient response to ursodeoxycholic acid. Further investigations of MM in PBC and overlap seem warranted. As first-line therapy for AIH, one randomised controlled study indicates that budesonide with AZA induces more remission with less side-effects than prednisolone with AZA. However, despite the one prospective cohort with MM as first-line therapy in AIH, and the limitations of earlier studies, most evidence for first-line therapy in AIH still is with AZA and prednisolone. We therefore still consider prednisolone with AZA the first-line treatment in AIH and overlap syndromes until further randomised studies prove otherwise. In case of steroid side-effects, in the absence of cirrhosis, budesonide could be considered, although a prospective maintenance study against prednisolone is still lacking. As second-line therapy in case of AZA-intolerance in AIH, or for all overlap syndrome patients, MM with prednisolone appears useful, but not for AIH with AZA nonresponse. In contrast to AZA, MM is contraindicated in pregnancy.

Osteoporosis is not a feature unique to primary biliary cirrhosis (PBC) but is also found in other categories of liver disease. The principles developed for monitoring and treating postmenopausal osteoporosis can also be followed for patients with PBC. Monitoring of dietary intake of calcium and vitamin D serum levels is essential, and the threshold for initiating supplementation should be low. Bisphosphonates can be considered the most rational choice when specific therapy is required.

Summary Four patients with weight loss, jaundice, a sonolucent swelling of the pancreas, and multiple bile-duct strictures are described. These cases of sclerosing pancreato-cholangitis responded to steroid therapy.

Background and Study Aims: The present study was aimed at exploring the feasibility of diagnostic laparoscopy on a day-case basis in patients with liver disease. Patients and Methods: Retrospective analysis was carried out of 85 consecutive day-case laparoscopies performed between January 1990 and January 1994. During this period, patients were observed in day-care facilities for a period of three hours. Patients' perception and acceptance of the procedure were assessed using a postal questionnaire. Results: Laparoscopy was successful in 84 of the 85 patients ; adequate liver biopsies were obtained in 83 patients. In three cases, the procedure was converted to a one-night hospital admission because of pain (1), persistent sedation (1) and collapse (1). Abdominal skin hematomas were reported by eight patients, and fever by two. Serious complications were not observed. The majority of patients experienced no complaints, or minor ones, after the procedure, and they expressed a preference for an outpatient procedure in case a renewed investigation might be indicated. Compared with in-hospital procedures, day-case laparoscopy was associated with a 33% reduction in cost. Conclusions: Diagnostic laparoscopy, with the hospital stay reduced to three hours, can be performed safely as a day-case procedure in selected patients.

941 ALKALINE PHOSPHATASE VALUES ARE A SURROGATE MARKER IN PREDICTION OF TRANSPLANT FREE SURVIVAL IN PATIENTS WITH PRIMARY BILIARY CIRRHOSIS – AN INTERNATIONAL, COLLABORATIVE ANALYSIS W.J. Lammers, H.R. van Buuren, G.M. Hirschfield, A. Pares, T. Kumagi, L. Caballeria, P. Invernizzi, A. Lleo, P.M. Battezzati, C. Corpechot, A. Floreani, N. Cazzagon, M.J. Mayo, J.A. Talwalkar, M. Imam, A.K. Burroughs, G. Pieri, F. Nevens, A.L. Mason, R. Poupon, H.L.A. Janssen, K.D. Lindor, B.E. Hansen, Global PBC Study Group. Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Liver Centre, Toronto Western Hospital, Toronto, ON, Canada; Centre for Liver Research and NIHR Institute of Biomedical Research, University of Birmingham, Birmingham, UK; Liver Unit, Hospital Cĺinic, CIBERehd, IDIBAPS, Barcelona, Spain; Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy; Dept of Medicine, Surgery and Dentistry, Universita degli Studi di Milano, Milan, Italy; Service d’Hepatologie, Hopital Saint-Antoine, APHP, UPMC, Paris, France; Department of Surgical, Oncological and Gastroenterological, University of Padova, Padova, Italy; Digestive and Liver disease, UT Southwestern Medical Centre, Dallas, TX, Gastroenterology and Hepatology, Mayo Clinic, Rochester, MA, USA; The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, UK; Hepatology, University Hospitals Leuven, UKLeuven, Leuven, Belgium; Divison of Gastroenterology and Hepatology, University of Alberta, Edmonton, AB, Canada; Health Solutions, Arizona State University, Phoenix, AZ, USA E-mail: w.lammers@erasmusmc.nl