Clinical Case Summary

We report a case of Intrahepatic Cholestasis of Pregnancy (ICP) leading to a rejections of a living, related donor liver two years after the liver transplantation (LT). The 36yo patient underwent LT in November 2021 in Mongolia due to a HBV/HDV related liver cirrhosis. Until August 2024, she had normal test results when she presented with severe pruritus and jaundice at 16-17th week of her second pregnancy. The ICP was diagnosed after elevated total bile acids were detected. A medical pregnancy termination was induced with subsequent three sessions of plasmapheresis. The patient's condition deteriorated further before she received her second living, unrelated donor LT in December 2024.
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	2023.07.03- prior to pregnancy	2024.08.18- during the pregnancy	2024.09.30- A month after termination	2024.11.04	2025.02.02- Two months after re-transplantation
Total bilirubin (mg/dL) /norm 0-1.2/	1.5 N	17.6 H	20.2 H	40.6 H	0.73 N
GOT/GPT (IU/mL) /norm 0-40/	11.3/18.3 N	265.3/196.1 H	79.5/77.1 H	262.5/113.1 H	6.2/7.6 N
Total bile acids (umol/mL) /norm 0-10/		170.2 H	332 H		7 N

The explant histology stated a massive hepatocellular necrosis (fulminant), total bile duct loss, massive cholestasis (canalicular and intracellular), allograft arteriopathy: Foamy histiocytes in the intimal artery, Arteriosclerosis and Lumen narrowing. No genetic test was performed , either prior or after the LTs. The final diagnosis: An Intrahepatic Cholestasis of Pregnancy leading to a liver graft rejection.
The ICP is a relatively common pregnancy related condition (0.2-2% of pregnancies in Europe and Americas¹) that presents with jaundice and pruritus. The condition usually improves after delivery/termination. In rare cases elevated serum bile acid levels lead to fetal abnormalities or loss of pregnancy. Since the patients condition did not improve after the pregnancy termination in September, 2024, Progressive Familial Intrahepatic Cholestasis (PFIC) was suspected when she admitted her first pregnancy was also complicated by ICP. Better history taking is needed to prevent graft rejection due to bile acid transport dysfunction.

References

1- Williamson, C. and V. Geenes, Intrahepatic cholestasis of pregnancy. Obstet Gynecol, 2014. 124(1): p. 120-133

Introduction

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated metabolic and cardiovascular benefits in patients with type 2 diabetes (T2D). However, their potential effect on pancreatic cancer (PC) risk remains unclear.

Aims & Methods

We aimed to examine the association between SGLT-2i use and PC risk in T2D patients prescribed metformin. We conducted a retrospective cohort study using a territory-wide electronic healthcare database, retrieving adult patients (≥18 years) with T2D who initiated metformin between 2015 and 2022. The index date was the first metformin prescription during the study period. Patients were observed until PC, pancreatectomy, death, or study end date (December 31, 2022). Exclusion criteria included prior history of PC, IgG4 disease, pancreatectomy, or fewer than two HbA1c measurements during follow-up. The outcome and exposure of interest was PC and SGLT-2i use (including dapagliflozin, empagliflozin, canagliflozin and ertugliflozin), respectively. SGLT-2i exposure was defined as continuous use during 90-day entry period following the index date. Cox proportional hazards model with propensity score (PS) matching (1:2) on 28 covariates – age, sex, smoking, alcohol use, body mass index (BMI), diabetes duration and complications, glycemic control (in terms of time-weighted mean HbA1c), history of pancreatitis and cholangitis, comorbidities, and concomitant medication use (aspirin, statins, and other antidiabetic medications) – were used to estimate hazard ratios (HRs). Sensitivity analysis by treating medication use as time-varying variable was conducted to address immortal time bias.

Results

Among 144,468 matched patients (mean age:59.3±11.2 years; male:58.3%; 48,156 SGLT-2i users and 96,312 SGLT-2i non-users), 441 (0.31%) developed PC during a mean follow-up of 6.6±2.0years. The mean duration of SGLT-2i use was 2.1±1.6 years. SGLT-2i use was associated with lowered PC risk (aHR:0.43; 95% CI:0.34-0.55), irrespective of empagliflozin (aHR0.43; 95%CI: 0.33-0.57) or dapagliflozin use (aHR:0.33; 95% CI:0.22-0.49). When drug use was modelled as time-varying variables, the protective effect remained significant (aHR:0.35; 95% CI:0.15-0.78). Furthermore, a dose- and duration-dependent relationship was observed. The aHR was 0.88 (95% CI:0.84-0.92) per 100-cumulative defined daily dose (cDDD) increase in use, and 0.66 (95% CI:0.59-0.75) per 1-year increase in use. Subgroup analysis showed beneficial effects persistent regardless of age (cutoff of 65 years), sex, BMI (cutoff of 25 kg/m²), diabetes complications, usage of other medications (aspirin, statins, and insulin).

Conclusion

SGLT-2i use was associated with a lower risk of PC in a dose- and duration-dependent manner, which was independent of glycemic control, among T2D patients treated with metformin. These findings provide insights into informing the choice of second-line anti-diabetic drug in lowering PC risk in T2D metformin users.

Introduction

Lumen-apposing metal stents (LAMSs) have significantly advanced endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs). However, their impact on clinical outcomes in real-world settings remains incompletely understood.

Aims & Methods

Using the Diagnosis Procedure Combination database—a nationwide inpatient database in Japan where LAMSs were approved in 2018—we identified 5,885 patients who underwent EUS-guided treatment for PFCs at 550 hospitals between 2010 and 2023. We examined the association between treatment period (before vs. after LAMS implementation at each hospital) and clinical outcomes. Multivariable logistic regression analyses were conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital mortality, bleeding, length of stay, and total healthcare costs, adjusting for potential confounders.

Results

Compared with patients treated in the pre-LAMS period, those treated in the post-LAMS period had a significantly higher risk of bleeding (adjusted OR, 1.56; 95% CI, 1.35–1.81). Additionally, the post-LAMS period was associated with an increase of approximately $3,300 (USD) in total healthcare costs, with an adjusted OR for being in the highest quartile of total costs of 1.55 (95% CI, 1.34–1.79). There was no significant difference in the risk of in-hospital mortality (adjusted OR, 1.21; 95% CI, 0.95–1.55) or prolonged hospitalisation (adjusted OR for top quartile, 0.98; 95% CI, 0.86–1.12).

Conclusion

The introduction of LAMSs was associated with an increased risk of bleeding and higher healthcare costs, without significant improvements in mortality or hospital stay duration. These findings suggest that routine use of LAMSs for EUS-guided PFC treatment should be reconsidered.

Disclosure

HI declares research funding from Boston Scientific Japan, Fujifilm, and Piolax Medical Devices; honoraria from Boston Scientific Japan, Century Medical, Create Medic, Fujifilm, Gadelius Medical, Hitachi Medical, Japan Lifeline, Kaneka, Kawasumi Laboratories, Olympus Medical, Piolax Medical Devices, Sumitomo Bakelite, UMIDAS, and Zeon Medical; and contributions from Boston Scientific Japan, Gadelius Medical, Japan Lifeline, and Zeon Medical. YN declares research funding from Boston Scientific Japan, Century Medical, Fujifilm, Gadelius Medical, HOYA Pentax Medical, Hitachi Medical, Kaneka, and Medico’s Hirata; and honoraria from Boston Scientific Japan, Fujifilm, Gadelius Medical, Hitachi Medical, J-MIT, Medico’s Hirata, and Olympus Medical. This work was not supported by any of those companies. No other conflicts of interest exist. The other authors declare that they have no conflicts of interest.

Introduction

Autoimmune pancreatitis (AIP) is a rare, immune-mediated form of chronic pancreatitis, classified into three subtypes. Type 1 AIP, the pancreatic manifestation of IgG4-related disease, often presents with multisystem involvement and frequent relapse (1,2). Type 2 AIP is pancreas-limited, tends to affect younger individuals, and is commonly associated with inflammatory bowel disease (IBD) (2,3). A third form—checkpoint inhibitor-related pancreatitis (CIP or Type 3 AIP)—has been recently described in patients receiving immune checkpoint inhibitors, typically asymptomatic but may result in pancreatic atrophy (4).
Precise subtyping is critical due to differences in clinical behavior, relapse risk, and treatment response (1,2,3). We present a single-center series comparing clinical, radiologic, and histopathologic characteristics of Type 1 and Type 2 AIP.

Aims & Methods

We retrospectively reviewed 20 patients diagnosed with AIP between 2020–2024 at a tertiary center. Classification followed International Consensus Diagnostic Criteria (1). Diagnostic evaluation included endoscopic ultrasound (EUS), serum IgG4 levels, and contrast-enhanced CT/MRI/MRCP (1,2). EUS-guided fine-needle biopsy (FNB) was performed where malignancy could not be excluded. Histopathology differentiated lymphoplasmacytic sclerosing pancreatitis (LPSP, Type 1) from idiopathic duct-centric pancreatitis (IDCP, Type 2) (2). Data on extra-pancreatic involvement, steroid response, and relapse were collected.

Results

Fifteen patients were diagnosed with Type 1 AIP and five with Type 2. Type 1 patients had a mean age of 63 years and were predominantly male (80%). Obstructive jaundice was the most common presentation. All had elevated serum IgG4. EUS revealed diffusely hyperechoic parenchyma and long-segment ductal narrowing. Histology confirmed LPSP. Extra-pancreatic involvement was observed in 60%, most commonly IgG4 cholangitis. All responded to corticosteroids; 40% relapsed within one year and received rituximab (5).
Type 2 patients had a mean age of 38, with equal gender distribution. Presenting symptoms included abdominal pain and acute pancreatitis. Serum IgG4 was normal in all cases. EUS revealed focal hypoechoic lesions with short-segment narrowing. Histology confirmed IDCP. Two patients (40%) had ulcerative colitis. All achieved remission with steroids, and no relapses were observed (2,3).

Conclusion

This series emphasizes the distinct clinical courses of AIP subtypes. Type 1 AIP represents a systemic IgG4-related disease with high relapse risk, often requiring long-term immunosuppression (5). Type 2 AIP affects younger patients, remains confined to the pancreas, and shows sustained remission after steroid therapy (2,3). Accurate classification using EUS, MRCP, IgG4, and histology is crucial for appropriate management and long-term outcomes (1,2).

References

1. Hart PA, Zen Y, Chari ST. Recent Advances in Autoimmune Pancreatitis. Gastroenterology. 2015;149(1):39–51.

2. de Pretis N, Crinò SF, Amodio A, et al. Type 2 autoimmune pancreatitis: Clinical features and long-term follow-up in an Italian cohort. United European Gastroenterol J. 2024;12(1):50–59.
   

3. Lohr JM, Dominguez-Munoz E, Rosendahl J, et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European Gastroenterol J.2017;5(2):153–199.

4. Lamarca A, Dhani N, Hubner RA, et al. Immune checkpoint inhibitor-induced autoimmune pancreatitis (Type 3 AIP): Emerging entity with distinct features. Ann Oncol. 2023;34(3):385–393.
   

5. Ghazale A, Chari ST, Zhang L, et al. Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: The Mayo Clinic experience. Clin Gastroenterol Hepatol. 2012;10(6):640–646.