H. R. van Buuren

The role of mycophenolate mofetil in the management of autoimmune hepatitis and overlap syndromes

Aliment Pharmacol Ther 2011; 34: 335–343

Epidemiology and clinical characteristics of autoimmune hepatitis in the Netherlands

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.

Prevalence of Autoimmune Pancreatitis and Other Benign Disorders in Pancreatoduodenectomy for Presumed Malignancy of the Pancreatic Head

BackgroundOccasionally 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.MethodsAll 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.ResultsA total of 274 PDs were performed for presumed malignancy. The prevalence of benign disease was 8.4xa0%, overall prevalence of AIP was 2.6xa0%. 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.ConclusionsThe prevalence of benign disease in patients who underwent PD for presumed malignancy was 8.4xa0%, 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.

Potential Value of Serum Total IgE for Differentiation between Autoimmune Pancreatitis and Pancreatic Cancer

Autoimmune pancreatitis (AIP) is associated with a marked elevation of serum total IgG4. Although there is evidence of autoimmunity in AIP, there are also signs of an allergic nature of its pathogenesis. Therefore, we determined both IgE and IgG4 in 13 patients with AIP, in 12 patients with pancreatic carcinoma and in 14 patients with atopic allergy and investigated the relationship between IgE and IgG4. Total IgG4 was determined by automated nephelometry and total IgE by automated enzyme fluoroimmunoassay. Both total IgE and total IgG4 levels in patients with AIP were significantly higher than those in patients with pancreatic carcinoma (Pu2003=u20030.0004 and Pu2003=u20030.015, respectively). There was a significant correlation between the total IgE and total IgG4 levels in patients with AIP and patients with atopic allergy (rsu2003=u20030.82,Pu2003=u20030.0006 and rsu2003=u20030.88,Pu2003<u20030.0001, respectively). The IgE/ IgG4 ratio in sera from patients with atopic allergy was significantly different (Pu2003=u20030.0012) from this ratio in sera from patients with AIP. These results suggest that analysis of total IgE in serum might be useful in the differentiation between autoimmune pancreatitis and pancreatic carcinoma.

Serum Level of Ca 19-9 Increases Ability of IgG4 Test to Distinguish Patients with Autoimmune Pancreatitis from Those with Pancreatic Carcinoma

BackgroundAutoimmune 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 (>1.4xa0g/l) are characteristic of AIP. We investigated whether serum levels of these proteins can differentiate between these diseases.MethodsWe 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.ResultsLow levels of Ca 19-9 were independently associated with AIP, compared with pancreatic adenocarcinoma [odds ratio (OR) 0.28; 95xa0% confidence interval (CI) 0.13–0.59; pxa0=xa00.0001]. Using an upper level of 74xa0U/ml, the assay for Ca 19-9 identified patients with AIP with 73xa0% sensitivity and 74xa0% specificity. Using a lower level of 2.6xa0g/l, the assay for IgG4 identified these patients with 70xa0% sensitivity and 100xa0% specificity. Combining data, levels of Ca 19-9xa0<xa074xa0U/ml and IgG4xa0>xa01.0xa0g/l identified patients with AIP with 94xa0% sensitivity and 100xa0% specificity.ConclusionsPatients 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 19-9xa0<xa074xa0U/ml and IgG4xa0>xa01.0xa0g/l distinguishes patients with AIP from those patients with pancreatic carcinoma with 94xa0% sensitivity and 100xa0% specificity.

Trans jugular Intrahepatic Portosystemic Shunt

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 ...

P1177 : Risk factors for hepatic decompensation in primary biliary cirrhosis - results of an international follow up study of 2326 patients

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.

5 Bestaat er een relatie tussen pancreatitis en prostatitis

Introductie IgG4-gerelateerde ziekte (IgG4-RD) is een zeldzame systeemziekte die wordt gekarakteriseerd door een verhoogde waarde van IgG4 in het serum, toegenomen IgG4-positieve plasmacellen in het weefsel en een goede respons op prednisonbehandeling. De meest voorkomende uiting is de auto-immuun pancreatitis (AIP). Doel van deze studie was het evalueren van het voorkomen en de histopathologische karakteristieken van IgG4-gerelateerde prostaataandoening bij patiënten met de diagnose AIP.

Mycophenolate mofetil for patients with autoimmune hepatitis and overlap syndromes : authors' reply

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. nFor all patients with overlap syndromes, MM appears a valuable treatment option. In the DAHG cohort, MM induced remission in 63% and 57%, and nresponse 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. nAs 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 nsyndromes 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. nAs second-line therapy in case of AZA-intolerance in AIH, or for all overlap nsyndrome patients, MM with prednisolone appears useful, but not for AIH with AZA nonresponse. In contrast to AZA, MM is contraindicated in pregnancy.