Frequency and risk factors for liver disease following pancreatitis: A population-based cohort study.

BACKGROUND & AIMS: Both liver disease (LD) and pancreatitis pose substantial burdens. There have been no general population-based studies on frequency of LD after an episode of pancreatitis. The aim of this study was to investigate the occurrence of LD in a population-based cohort of patients following pancreatitis. METHODS: Nationwide data on the general population of nearly 3 million people were used to identify retrospectively diagnoses of acute pancreatitis, chronic pancreatitis (CP), LD and cirrhosis from 1998 to 2016. Acute pancreatitis was categorised as first (FAP) or recurrent (RAP) episode. Number of pancreatitis recurrences prior to LD diagnosis was determined. RESULTS: A total of 20,931 pancreatitis patients were included, of which 874 developed LD following pancreatitis. The incidence of LD in FAP was 115.59 (95% confidence interval 102.19-128.98), in RAP - 217.63 (95% confidence interval 173.31-261.94), and in CP - 539.43 (95% confidence interval 494.72-584.13) patients per 100,000 pancreatitis patients per year. There was a significant increase in the probability of LD with increasing number of pancreatitis recurrences and, for the same number of pancreatitis recurrences, LD was significantly more frequent after CP than RAP (hazard ratio 1.666 (95% confidence interval 1.322-2.098; p = <0.001)). CONCLUSIONS: The frequency of LD increases from FAP to RAP to CP. While number of pancreatitis recurrences is a significant risk factor for development of LD, there is a higher probability of LD following CP than RAP even for the same number of recurrences. Interventions preventing pancreatitis and its progression may lower the burden of LD.

Post-pancreatitis diabetes mellitus: towards understanding the role of gastrointestinal motility.

Post-pancreatitis diabetes mellitus (PPDM) is a sub-type of diabetes of the exocrine pancreas that develops after acute or chronic inflammation of the pancreas. While pro-inflammatory milieu, glucose metabolism, and lipid metabolism in PPDM have been investigated, little is known about gastrointestinal function in the post-pancreatitis setting. This article overviews studies on epidemiology and impact of gastroparesis in the setting of type 1 and type 2 diabetes, with a view to estimating the possible burden of gastrointestinal dysfunction in PPDM. Further, the usefulness of quantifying gastrointestinal dysmotility is discussed. The gastroparesis cardinal symptom index has emerged as a standardized gastrointestinal dysmotility endpoint and its use in individuals after pancreatitis is justified.

Iron: a Strong Element in the Pathogenesis of Chronic Hyperglycaemia After Acute Pancreatitis.

Evidence shows an association between markers of iron metabolism and glucose metabolism in type 2 diabetes mellitus. Acute pancreatitis is the largest contributor to diabetes of the exocrine pancreas. However, the pathogenesis of new-onset pre-diabetes or diabetes after pancreatitis remains unclear. This study aimed to investigate associations between markers of iron metabolism and glucose metabolism following acute pancreatitis. Fasting blood samples were collected to analyse markers of glucose metabolism (haemoglobin A1c) and iron metabolism (hepcidin, ferritin, and soluble transferrin receptor). Participants were categorised into two groups: normoglycaemia after acute pancreatitis and chronic hyperglycaemia after acute pancreatitis. Binary logistic and linear regression analyses were conducted, and potential confounders were adjusted for in multivariable analyses. A total of 83 individuals following an episode of acute pancreatitis were included, of whom 19 developed chronic hyperglycaemia. Hepcidin was significantly increased in individuals with chronic hyperglycaemia after acute pancreatitis in two adjusted models (p = 0.045 and p = 0.048). Ferritin was significantly decreased in individuals with chronic hyperglycaemia after acute pancreatitis in three adjusted models (p = 0.016, p = 0.009, and p = 0.011). Soluble transferrin receptor was not significantly associated with chronic hyperglycaemia after acute pancreatitis. These findings suggest that iron metabolism is significantly altered in individuals with chronic hyperglycaemia after acute pancreatitis and may provide better insights into the pathogenesis of new-onset diabetes after pancreatitis.

Pro-inflammatory cytokines after an episode of acute pancreatitis: associations with fasting gut hormone profile.

INTRODUCTION: Pro-inflammatory cytokines, such as interleukin (IL)-6, tumour necrosis factor (TNF)α, and monocyte chemoattractant protein (MCP)-1, are often elevated in individuals after acute pancreatitis but what determines their levels is poorly understood. Gut hormones have emerged as possible modulators of inflammatory response. The aim was to investigate the associations between pro-inflammatory cytokines and a comprehensive panel of gut hormones after an episode of acute pancreatitis. MATERIALS AND METHODS: Fasting blood samples were collected to measure cytokines (IL-6, TNFα, and MCP-1) and gut hormones (cholecystokinin, gastric inhibitory peptide (GIP), ghrelin, glicentin, glucagon-like peptide-1, oxyntomodulin, peptide YY, secretin, and vasoactive intestinal peptide). A series of linear regression analyses was conducted and four statistical models were used to adjust for patient- and pancreatitis-related covariates. RESULTS: A total of 83 individuals were recruited. GIP and peptide YY were significantly (p < 0.001) associated with IL-6, TNFα, MCP-1, consistently in all the four models. Every 1 ng/mL change in GIP resulted in a 16.2, 3.2, and 50.8% increase in IL-6, TNFα, and MCP-1, respectively, in the most adjusted model. Every 1 ng/mL change in peptide YY resulted in a 7.0, 2.4, and 32.1% increase in IL-6, TNFα, and MCP-1, respectively, in the most adjusted model. GIP independently contributed 29.0-36.5% and peptide YY - 17.4-48.9% to circulating levels of the studied pro-inflammatory cytokines. The other seven studied gut hormones did not show consistently significant associations with pro-inflammatory cytokines. CONCLUSIONS: GIP and peptide YY appear to be involved in perpetuation of subclinical inflammation following an episode of acute pancreatitis, which is known to play an important role in the pathogenesis of blood glucose derangements. These findings advance the understanding of mechanisms underlying diabetes of the exocrine pancreas and have translational implications.

Interplay between innate immunity and iron metabolism after acute pancreatitis.

Emerging evidence shows that chronic low-grade inflammation and changes in markers of innate immunity are implicated in a range of metabolic abnormalities following an episode of acute pancreatitis. Also, deranged iron metabolism has been linked to type 2 diabetes mellitus, gestational diabetes, and new-onset diabetes after pancreatitis - the conditions characterized by high haemoglobin glycation index (HGI). This study aimed to investigate the associations between markers of innate immunity and iron metabolism in individuals after acute pancreatitis. Fasting blood samples were collected to analyse lipopolysaccharide binding protein (LBP), interleukin (IL)-6, tumor necrosis factor-α, hepcidin, ferritin, soluble transferrin receptor, HbA1c, and glucose. Participants were categorized into two groups: low HGI and high HGI. Linear regression analyses were conducted, and potential confounders (age, sex, ethnicity, body mass index, diabetes mellitus status, smoking status, aetiology of pancreatitis, duration, recurrence, and severity of pancreatitis) were adjusted for in 5 statistical models. A total of 93 patients following an episode of acute pancreatitis were included, of who 40 (43%) had high HGI. In the overall cohort, LBP was significantly associated with hepcidin and ferritin, and IL-6 was significantly associated with hepcidin, consistently in all the models. Further, LBP contributed to 7.7% and 9.5% of variance in hepcidin and ferritin levels, respectively, whereas IL-6 contributed to 5.3% of hepcidin variance. Upon subgroup analysis, the observed LBP associations were maintained in the high HGI subgroup only and the IL-6 association in the low HGI subgroup only. No consistently significant associations were found between any of the other markers. The interplay between LBP, IL-6, hepcidin, and ferritin characterizes metabolic derangements after acute pancreatitis and may play a role in the pathogenesis of new-onset diabetes after pancreatitis.