Marianne J. Van Heerde

Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4‐associated cholangitis from primary sclerosing cholangitis

The recent addition of immunoglobulin (Ig)G4‐associated cholangitis (IAC), also called IgG4‐related sclerosing cholangitis (IRSC), to the spectrum of chronic cholangiopathies has created the clinical need for reliable methods to discriminate between IAC and the more common cholestatic entities, primary (PSC) and secondary sclerosing cholangitis. The current American Association for the Study of Liver Diseases practice guidelines for PSC advise on the measurement of specific Ig (sIg)G4 in PSC patients, but interpretation of elevated sIgG4 levels remains unclear. We aimed to provide an algorithm to distinguish IAC from PSC using sIgG analyses. We measured total IgG and IgG subclasses in serum samples of IAC (n = 73) and PSC (n = 310) patients, as well as in serum samples of disease controls (primary biliary cirrhosis; n = 22). sIgG4 levels were elevated above the upper limit of normal (ULN = >1.4 g/L) in 45 PSC patients (15%; 95% confidence interval [CI]: 11‐19). The highest specificity and positive predictive value (PPV; 100%) for IAC were reached when applying the 4× ULN (sIgG4 > 5.6 g/L) cutoff with a sensitivity of 42% (95% CI: 31‐55). However, in patients with a sIgG4 between 1× and 2× ULN (n = 38/45), the PPV of sIgG4 for IAC was only 28%. In this subgroup, the sIgG4/sIgG1 ratio cutoff of 0.24 yielded a sensitivity of 80% (95% CI: 51‐95), a specificity of 74% (95% CI: 57‐86), a PPV of 55% (95% CI: 33‐75), and a negative predictive value of 90% (95% CI: 73‐97). Conclusion: Elevated sIgG4 (>1.4 g/L) occurred in 15% of patients with PSC. In patients with a sIgG4 >1.4 and <2.8 g/L, incorporating the IgG4/IgG1 ratio with a cutoff at 0.24 in the diagnostic algorithm significantly improved PPV and specificity. We propose a new diagnostic algorithm based on IgG4/IgG1 ratio that may be used in clinical practice to distinguish PSC from IAC. (Hepatology 2014;59:1954–1963)

Comparable efficacy of low- versus high-dose induction corticosteroid treatment in autoimmune pancreatitis.

Objective The objective of this study was to compare efficacy of high versus low doses of prednisone for induction of remission in autoimmune pancreatitis (AIP). Methods This is a retrospective, multicenter study including patients diagnosed with AIP between May 1992 and August 2011. Clinical, laboratory and imaging findings were assessed before treatment and at 1, 3, and 6 months after starting treatment. Results A total of 65 patients (57 males; median age, 63 years) were treated with an initial low dose (10–20 mg/d, n = 14), a medium dose (30 mg/d, n = 15), or a high dose (40–60 mg/d, n = 36) of prednisone. There were no significant differences in baseline characteristics between the treatment groups including age, presenting symptoms and laboratory results. During a follow-up period of 6 months, in nearly all patients, symptoms (jaundice, weight loss) resolved completely. After 6 months, treatment response with respect to symptomatic, radiological, and laboratory improvement was comparable for the different dosage groups. Conclusions Response to therapy was comparable for AIP patients treated with doses of prednisone in the range of 10 to 60 mg/d. A prospective trial should be conducted to confirm efficacy of lower-dose prednisone treatment.

The Long-Term Impact of Autoimmune Pancreatitis on Pancreatic Function, Quality of Life, and Life Expectancy

Objective To evaluate the long-term outcome of autoimmune pancreatitis. Methods Patients with at least 2 years of follow-up were included. Information was collected regarding disease characteristics, treatment outcome, diagnosed malignancies, and mortality. In addition, pancreatic function and quality of life were assessed prospectively. Results 107 patients were included (87% men, 90% with type 1), with a median follow-up of 74 (interquartile range, 49–108) months. One third was operated for suspected pancreatic cancer (32%). Most patients were (successfully) treated with steroids (83%), but relapses were common (52%), for which no risk factors could be identified. Pancreatic carcinoma was not observed. Prospective data were obtained from 64%, as 17% had died, 7% were lost to follow-up, and 13% refused to participate. After a median of 75 (interquartile range, 50–106) months, 46% still used active treatment. Exocrine and endocrine insufficiencies were highly prevalent (82% and 57%, respectively). Quality of life and survival were not impaired, as compared with a reference population. Conclusions Despite an excellent initial treatment response, relapses are common, even in type 2, and almost half of the patients require maintenance therapy. Pancreatic insufficiency is highly prevalent, which calls for active screening. Pancreatic cancer was not observed, and quality of life and survival are not impaired.

A comparative study of diagnostic scoring systems for autoimmune pancreatitis

Objective Several diagnostic scoring systems for autoimmune pancreatitis (AIP) have been proposed including the Asian, HISORt (Histology, Imaging, Serology, Other organ involvement and Response to therapy), and International Consensus Diagnostic Criteria (ICDC), which have been compared by a few studies. We evaluated the diagnostic performance of these criteria in patients diagnosed with AIP between May 1992 and August 2011. Methods Scoring systems were applied retrospectively using data obtained in the initial evaluation period, before pancreatic resection was performed. Results One hundred fourteen cases with AIP were included. Eighty-two percent met the diagnostic criteria for AIP according to either the Asian, HISORt, or ICDC criteria. Only 33% met the Asian criteria, probably mainly related to a low rate of diagnostic pancreatography. In 18%, all scoring systems failed to confirm the diagnosis, even though these patients were considered to have a firm diagnosis of AIP. Conclusions In this cohort of AIP patients, the 3 major diagnostic scoring systems for AIP proved to be complementary rather than overlapping. Our data indicate that one-fifth of our AIP patients do not meet any of these scoring systems. The ICDC, Asian, and HISORt criteria should be considered as useful clinical tools but not as criterion standard for the diagnosis.

Testing for Anti-PBP Antibody Is Not Useful in Diagnosing Autoimmune Pancreatitis.

OBJECTIVES:Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, clinically mimicking pancreatic cancer. In 2009, a serological diagnostic test detecting antibodies against plasminogen-binding protein (PBP) of Helicobacter pylori was reported with outstanding test performances (NEJM 361:135). We aimed to validate these findings.METHODS:Between March 2007 and May 2011, sera were collected from consecutive patients presenting with type 1 AIP, pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), primary sclerosing cholangitis (PSC), and healthy controls (HC) with or without antibodies against H. pylori. Serum antibody binding to synthetic PBP peptide was quantified by enzyme-linked immunosorbent assay (ELISA), using standard curves of custom-made PBP rabbit polyclonal antibodies. A synthetic Flag peptide (DYKDDDK), to which no antibodies are found in human serum, was included as negative control.RESULTS:High sensitivity of PBP peptide recognition was demonstrated by selective binding of PBP peptide over Flag peptide by PBP-immunized rabbit serum. Competition assays with PBP peptide validated the selectivity for antibodies recognizing this antigen. A total of 114 patients were subsequently tested: 34 AIP, 29 PDAC, 17 CP, 16 PSC, and 18 HCs (9 positive and 9 negative for H. pylori). No significant differences in detection of antibodies against the PBP peptide were found between different the patient groups and healthy controls.CONCLUSIONS:Using a sensitive and selective ELISA-based assay, we did not find increased serum antibodies against PBP peptide in AIP patients. PBP serum antibodies are therefore not a useful diagnostic tool to diagnose AIP.

Tu1483 Anti-PBP Antibodies Not Usefull to Identify Autoimmune Pancreatitis in Dutch Cohort

to respond to initial steroids, and 12 experienced a relapse (average time to relapse was 577 +/-799 days). Among patients who failed the steroid taper or who relapsed, 10 were treated with a second course of prednisone, 6 with azathioprine, 1 with rituximab, 1 with mycophenolate, and 3 remained on low-dose steroids indefinitely. Among AIP2 patients, one failed to taper steroids and remains on low-dose indefinitely, but no relapses have been observed. Rates of endoscopic balloon dilation of strictures and stenting varied between AIP1 and 2 patients (21 vs 25%, and 96 vs 75%, respectively), but were not statistically significant. Conclusions: 1) AIP1 and 2 patients varied demographically and by baseline lab values. 2) Improved early diagnostic testing may reduce the number of surgeries. 3) Over a third of AIP1 patients did not respond or relapsed after initial prednisone treatment. 4) Despite a smaller AIP2 cohort size and shorter clinical follow up, our data suggest AIP1 patients may require more aggressive initial and recurrent medical management.