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Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort.

Huggett MT, Culver EL, Kumar M, Hurst JM, Rodriguez-Justo M, Chapman MH, Johnson GJ, Pereira SP, Chapman RW, Webster GJ, Barnes E - Am. J. Gastroenterol. (2014)

Bottom Line: The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio=2.25, CI=1.12-3.94, P=0.02).Mortality occurred in 10% of patients during follow-up.The risk of death was increased compared with matched national statistics (odds ratio=2.07, CI=1.07-3.55, P=0.02).

View Article: PubMed Central - PubMed

Affiliation: 1] UCL Institute for Liver and Digestive Health, University College London, London, UK [2] Department of Gastroenterology and Hepatology, University College Hospital, London, UK [3] M.T. Huggett and E.L. Culver contributed equally to this work.

ABSTRACT

Objectives: Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers.

Methods: Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1-107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics.

Results: Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P<0.01). Malignancy occurred in 11% shortly before or after the diagnosis of IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio=2.25, CI=1.12-3.94, P=0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio=2.07, CI=1.07-3.55, P=0.02).

Conclusions: Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up.

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Related in: MedlinePlus

Fibro-inflammatory changes in the liver. Liver biopsy (a: hematoxylin and eosin (H&E), ×40 and b: reticulin, ×40) showing thick fibrous bands with nodule formation. Inflammatory cell infiltrate rich in lymphocytes and plasma cells (c: H&E ×400). Large number of plasma cells expressing IgG4 (d: IgG4, ×400; inset: CD138, ×200).
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Figure 2: Fibro-inflammatory changes in the liver. Liver biopsy (a: hematoxylin and eosin (H&E), ×40 and b: reticulin, ×40) showing thick fibrous bands with nodule formation. Inflammatory cell infiltrate rich in lymphocytes and plasma cells (c: H&E ×400). Large number of plasma cells expressing IgG4 (d: IgG4, ×400; inset: CD138, ×200).

Mentions: Six patients (5%) developed liver cirrhosis during follow-up. Cirrhosis was diagnosed on liver biopsy in two patients (Figure 2), and clinically in four patients (patients with signs of synthetic dysfunction and/or hepatic decompensation with consistent radiology). One patient underwent a successful liver transplantation. With regard to specific pancreatic complications, exocrine insufficiency occurred in 53% of patients, which was determined by measurement of fecal elastase (defined as < 200 μg in a solid stool sample; measured in 114 patients) and diabetes in 37%. Diabetes was pre-existent before steroid therapy in 89% of the diabetic patients. Twelve percent of patients developed biochemical renal impairment, ranging from stage 2 to 4 kidney disease. Portal and/or splenic vein thrombosis developed in 9%, but with no evidence of variceal bleeding in any patients. A list of non-malignant complications is shown in Table 2.


Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort.

Huggett MT, Culver EL, Kumar M, Hurst JM, Rodriguez-Justo M, Chapman MH, Johnson GJ, Pereira SP, Chapman RW, Webster GJ, Barnes E - Am. J. Gastroenterol. (2014)

Fibro-inflammatory changes in the liver. Liver biopsy (a: hematoxylin and eosin (H&E), ×40 and b: reticulin, ×40) showing thick fibrous bands with nodule formation. Inflammatory cell infiltrate rich in lymphocytes and plasma cells (c: H&E ×400). Large number of plasma cells expressing IgG4 (d: IgG4, ×400; inset: CD138, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4552254&req=5

Figure 2: Fibro-inflammatory changes in the liver. Liver biopsy (a: hematoxylin and eosin (H&E), ×40 and b: reticulin, ×40) showing thick fibrous bands with nodule formation. Inflammatory cell infiltrate rich in lymphocytes and plasma cells (c: H&E ×400). Large number of plasma cells expressing IgG4 (d: IgG4, ×400; inset: CD138, ×200).
Mentions: Six patients (5%) developed liver cirrhosis during follow-up. Cirrhosis was diagnosed on liver biopsy in two patients (Figure 2), and clinically in four patients (patients with signs of synthetic dysfunction and/or hepatic decompensation with consistent radiology). One patient underwent a successful liver transplantation. With regard to specific pancreatic complications, exocrine insufficiency occurred in 53% of patients, which was determined by measurement of fecal elastase (defined as < 200 μg in a solid stool sample; measured in 114 patients) and diabetes in 37%. Diabetes was pre-existent before steroid therapy in 89% of the diabetic patients. Twelve percent of patients developed biochemical renal impairment, ranging from stage 2 to 4 kidney disease. Portal and/or splenic vein thrombosis developed in 9%, but with no evidence of variceal bleeding in any patients. A list of non-malignant complications is shown in Table 2.

Bottom Line: The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio=2.25, CI=1.12-3.94, P=0.02).Mortality occurred in 10% of patients during follow-up.The risk of death was increased compared with matched national statistics (odds ratio=2.07, CI=1.07-3.55, P=0.02).

View Article: PubMed Central - PubMed

Affiliation: 1] UCL Institute for Liver and Digestive Health, University College London, London, UK [2] Department of Gastroenterology and Hepatology, University College Hospital, London, UK [3] M.T. Huggett and E.L. Culver contributed equally to this work.

ABSTRACT

Objectives: Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers.

Methods: Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1-107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics.

Results: Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P<0.01). Malignancy occurred in 11% shortly before or after the diagnosis of IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio=2.25, CI=1.12-3.94, P=0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio=2.07, CI=1.07-3.55, P=0.02).

Conclusions: Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up.

Show MeSH
Related in: MedlinePlus