Introduction

Accurately predicting the severity of acute pancreatitis (AP) is a challenge in clinical practice. Recent advancements in artificial intelligence and neural network computing enable the use of CT scans for body composition analysis in addition to their diagnostic role. However, the prognostic application of various CT metrics has been inconsistent, resulting in conflicting data regarding the most reliable indicators of disease severity.

Aims & Methods

Our study aimed to evaluate the key CT body composition metrics for predicting severity in patients with acute pancreatitis (AP). We conducted a retrospective analysis of 279 AP patients from the University of Pécs, Hungary, all of whom underwent a CT scan within the first 24 hours of admission to the Department of Gastroenterology. Using the TotalSegmentator tool¹ of the 3D Slicer software, we measured the areas of visceral and subcutaneous adipose tissues (VAT and SAT) and skeletal muscle (SMA) at the level of the third lumbar vertebra (L3), with the results in square centimeters. These area measurements were then normalized for patient height by dividing them by the square of the patient's height to produce indices similar to the Body Mass Index (BMI), namely the VATI (Visceral Adipose Tissue Index), SATI (Subcutaneous Adipose Tissue Index), and SMI (Skeletal Muscle Index). We also quantified the average muscle radio-density in Hounsfield Units (HU), indicative of fatty muscle infiltration - associated with lower density values. We explored these metrics as potential predictors of severe AP, as defined by the Revised Atlanta Criteria². To assess predictive accuracy, we created receiver operating characteristic (ROC) curves and computed the area under the curve (AUC) for both genders separately due to inherent differences in normal values. The actual clinical progression of AP in these patients provided the reference standard. All statistical analyses were done using IBM SPSS Statistics software; preliminary results are available below.

Results

The data encompassed 174 male and 105 female patients, with an AP severity distribution of 139 mild, 116 moderately severe, and 24 severe cases. The AUC values for various CT metrics, differentiated by gender, are displayed in the subsequent table.

Conclusion

CT-derived body composition metrics demonstrate substantial prognostic value in identifying severe AP. Index-based metrics demonstrated slightly improved accuracy over simple area measurements. Elevated levels of subcutaneous and visceral fat emerged as predictors of severe AP, as evidenced by the SAT, SATI, VAT, and VATI metrics. Furthermore, a decreased muscle radio-density was a better predictor of severity than the skeletal muscle area (SMA) or skeletal muscle index (SMI) alone. The combination of significant fat accumulation and skeletal muscle loss - often referred to as sarcopenic obesity - was also predictive of more severe AP. Determining the precise cutoff values for these metrics to optimize predictive accuracy continues to be a key objective of our ongoing research.

References

1 - Wasserthal J, Breit HC, Meyer MT, Pradella M, Hinck D, Sauter AW, Heye T, Boll DT, Cyriac J, Yang S, Bach M, Segeroth M. TotalSegmentator: Robust Segmentation of 104 Anatomic Structures in CT Images. Radiol Artif Intell. 2023 Jul 5;5(5):e230024. doi: 10.1148/ryai.230024. PMID: 37795137; PMCID: PMC10546353.
2 - Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25. PMID: 23100216.

Disclosure

I have no conflicts of interest to disclose.

Introduction

A male patient in his twenties presented with clinical aspects of primary sclerosing cholangitis (PSC), chronic cholestatic liver disease, and hypothyroidism. PSC is a rare, chronic cholestatic liver disease characterized by biliary strictures and peribiliary fibrosis (1). Susceptible loci were identified in GWAS but the correlation between genetic background and disease pathogenesis needs further investigation (2). In the index patient we identified a heterozygote candidate variant in the ABCC6 gene (c.2279G>A, p.(Arg760Gln)). Dysfunctional ABCC6 was described to cause ABCB11 and ABCG5/G8 genes overexpression, leading to imbalanced bile composition resulting in gallstone formation and cholestasis (3). ABCC6 variants were previously described in cases with low phospholipid-associated cholelithiasis (LPAC) and intrahepatic cholestasis of pregnancy (ICP)(4-6) . Subsequently, we aimed to investigate rare variants in ABCC6 gene in whole exome sequencing (WES) results from patients with suspected cholestatic liver disease.

Aims & Methods

Variant evaluation and annotation analysis was carried out on WES data, with focus on loss of function and missense variants, presenting allele frequency (AF) of ≤1% based on gnomAD database (https://gnomad.broadinstitute.org). Variants were filtered to include only those in genes relevant to the patients’ clinical phenotype. For each rare variant, a comprehensive in silico assessment was performed using tools such as REVEL, AlphaMissense, EVE, SIFT, and MetaLR to evaluate potential pathogenicity. Filtered were prioritized and interpreted using ACMG-AMP guidelines. This systematic approach ensured a clinically meaningful and evidence-based evaluation of the identified variants.

Results

Nine different rare heterozygote variants were identified in fifteen samples of 247 WES results. Among these, the missense variants c.179G>A, p.(Arg60Gln) and c.3139C>T, p.(Arg1047Cys) were found in two LPAC patients. Additionally, the c.1171A>G, p.(Arg391Gly) variant was observed in two related cases: a mother with ICP and her child with elevated gamma-glutamyl transferase (GGT) levels and jaundice. Moreover, this variant was also detected in another patient with elevated transaminases. c.3871G>A, p.(Ala1291Thr) and c.955A>G, p.(Ile319Val) were seen in patients with ICP and cholestasis, respectively. Three other variants were also identified in patients with liver disease of unknown etiology (c.1540G>A, p.(Val514Ile) and c.2707G>C, p.(Glu903Gln) and c.4397G>A, p.CYS1466Tyr). Additionally one splicing variant (c.37-1G>A, p,?) was also detected in a patient with cholangiocarcinoma (CCA). All variants were observed in heterozygote state and classified as variants of uncertain significance (VUS).

Conclusion

An in-depth analysis of WES data led to the identification of several potentially disease-relevant variants in the ABCC6 gene. These variants may play a contributory role in the observed hepatic phenotypes, suggesting a broader functional involvement of ABCC6 beyond its well-established association with pseudoxanthoma elasticum (PXE). Our findings highlight the importance of integrating genetic data with detailed clinical phenotyping to enhance understanding of genotype–phenotype correlations and reveal novel roles for known genes in atypical or organ-specific presentations.

References

1. Reich M, Spomer L, Klindt C, Fuchs K, Stindt J, et al. Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis. J Hepatol. 2021;75(3):634-46.
2. Goode EC, Fachal L, Panousis N, Moutsianas L, McIntyre RE, Bai BYH, et al. Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci. Nat Commun. 2024;15(1):9594.
3. Ibold B, Faust I, Tiemann J, Gorgels T, Bergen AAB, Knabbe C, et al. Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues. Lipids Health Dis. 2019;18(1):2.
4. Liu X, Lai H, Xin S, Li Z, Zeng X, Nie L, et al. Whole-exome sequencing identifies novel mutations in ABC transporter genes associated with intrahepatic cholestasis of pregnancy disease: a case-control study. BMC Pregnancy Childbirth. 2021;21(1):110.
5. Liu X, Zheng J, Xin S, Zeng Y, Wu X, Zeng X, et al. Whole-exome sequencing expands the roles of novel mutations of organic anion transporting polypeptide, ATP-binding cassette transporter, and receptor genes in intrahepatic cholestasis of pregnancy. Front Genet. 2022;13:941027.
6. Romeo M, Dallio M, Federico A. Is it time to reconsider the MRP6 role in bile secretion and LPAC genetic signature? J Hepatol. 2023;79(4):e152-e4.

Disclosure

The authors declare that they have no conflict of interest.

Introduction

Pain is the hallmark and most disabling symptom of chronic calcific pancreatitis (CCP), often severe and significantly impairing patients' quality of life. Its pathophysiology involves increased intraductal pressure, chronic inflammation, and neuropathic changes.

Aims & Methods

This study aimed to assess the prevalence of pain in CCP and to identify factors associated with its occurrence and severity.
This was a retrospective analytical study including patients followed for CCP. We collected data on disease duration, etiology, clinical manifestations, complications, analgesic treatments (AT), and symptom evolution under treatment. Pain intensity and impact on quality of life were assessed using the Izbicki Score (IS), which categorizes pain as mild (0–20), moderate (21–40), severe (41–60), or very severe (>60). Incomplete records that prevented IS calculation were excluded. Data were entered and analyzed using SPSS software, with statistical significance set at p < 0.05.

Results

We included 22 patients (14 men and 8 women), with a mean age of 55.6 years [27–80 years]. The most common symptoms were epigastric pain (n=18), weight loss (n=13), and chronic diarrhea (n=6). The mean delay between symptom onset and diagnosis was 25 months [1–120 months]. Etiologies included hyperparathyroidism (n=6), alcohol use (n=2), pancreas divisum (n=2), autoimmune causes (n=2), and were undetermined in 10 cases. The IS ranged from 0 to 93.75, with a mean of 40.22. Eight patients had an IS >40. Morphine was required in four cases; paracetamol was prescribed for 12 patients, and tramadol for two. Endoscopic treatment was indicated in three cases, while one patient underwent a Wirsungojejunostomy.
In univariate analysis, alcohol consumption was significantly associated with the occurrence of epigastric pain (p=0.01). Smoking and alcohol use were both linked to a higher IS (>50) (p=0.04). Smoking cessation was associated with a better analgesic response (p=0.04). Morphine use was significantly more frequent among alcoholic patients (p=0.01), and their treatment response was often unfavorable (p=0.02).

Conclusion

In our cohort, 80% of patients with CCP experienced pain, which was severe to very severe in nearly half the cases. Pain intensity was significantly associated with tobacco and alcohol consumption, while cessation improved treatment response. These findings underscore the importance of therapeutic education focused on smoking and alcohol cessation, in addition to analgesic management, to slow disease progression and improve pain control.