Introduction

Patients with primary biliary cholangitis (PBC) are at an increased risk of developing cirrhosis and eventually experiencing hepatic decompensation. While there is increasing evidence for more prevalent aetiologies of cirrhosis that a successful removal/suppression of the underlying aetiological factor can induce significant improvements in liver function and even enable hepatic recompensation, similar insights in PBC are scarce.

Aims & Methods

In this study, we aimed to explore clinical implications of hepatic recompensation according to the novel Baveno VII criteria in PBC, while considering a biochemical response to ursodeoxycholic acid (UDCA) according to Paris-II criteria as surrogate marker of a successful aetiological treatment. Specifically, we included cirrhotic PBC patients at the time of first hepatic decompensation (ascites, hepatic encephalopathy [HE], variceal bleeding) and analysed their subsequent clinical disease course. In accordance with Baveno VII criteria, we defined hepatic recompensation as (i) resolution of ascites and HE despite discontinuation of diuretics and HE treatment, (ii) absence of variceal bleeding and (iii) sustained improvements in biochemical liver function.

Results

This study enrolled 42 PBC patients with decompensated cirrhosis (age: 63.5 [IQR:51.9-69.2] years; 88.1% female) who were followed-up for a median of 41.9 (IQR:11.0-70.9) months after decompensation. The cause of index decompensation was ascites in 54.8%, variceal bleeding in 35.7% and HE in 9.5% of cases. At time of decompensation, the median MELD-Na was 14 (IQR:11-15). Overall, 33 patients were treated with UDCA for at least 1 year (median dose: 12.5 [IQR:10.7-15.0] mg/kg) and 36% of those (12/33) achieved the Paris-II response criteria.
Over the course of the study, 7 patients (16.7%) achieved recompensation. In a competing risk model, baseline parameters linked to a higher probability of recompensation included a lower MELD-Na (SHR: 0.90; 0.047), a lower Child-Pugh score (SHR: 0.59; p=0.019), lower bilirubin (SHR: 0.44; p=0.005), lower alkaline phosphatase (SHR: 0.96; p=0.001) and variceal bleeding as index decompensation (SHR: 4.37; p=0.069). Interestingly, while 5/12 (42%) UDCA responders recompensated and a response at 1 year was linked to a higher probability of recompensation (SHR: 5.08; p=0.041), 2/21 (10%) patients without UDCA response still eventually achieved recompensation.
Regarding prognostic implications, recompensation was linked to a numerically improved transplant-free survival in a time-dependent Cox regression model (HR: 0.46; p=0.335). Specifically, 3 recompensated patients survived without any further complications or the need for liver transplantation over a follow-up time of 35, 40 and 294 months after recompensation. Nevertheless, the remaining 4 recompensated patients presented with liver-related complications after developing hepatic malignancies and/or portal vein thrombosis (PVT) and two eventually died (18 and 29 months after recompensation). In contrast, of the patients who remained decompensated, 10 underwent liver transplantation (29%) and 17 died (49%).

Conclusion

Patients with decompensated cirrhosis due to PBC may achieve hepatic recompensation under UDCA therapy, particularly if the degree of liver dysfunction at index decompensation is less pronounced. Nonetheless, recompensated patients should be monitored carefully for the development of hepatic malignancy and PVT, as liver transplantation may still be required.

Disclosure

Albert Friedrich Stättermayer: Speaker and/or consultant and/or advisory board member for Boehringer Ingelheim, Gilead, and MSD. Benedikt Simbrunner: Travel support from AbbVie and Gilead. Mattias Mandorfer: Speaker and/or consultant and/or advisory board member for AbbVie, Collective Acumen, Gilead, and W. L. Gore & Associates; Travel support from AbbVie and Gilead. Michael Trauner: Grant support from Albireo, Alnylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda and UltraGenyx; Honoraria for consulting from Albireo, Boehringer Ingelheim, BiomX, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex, Pliant, Regulus and Shire; Speaker fees from Bristol-Myers Squibb, Falk, Gilead, Intercept and MSD; Travel support from AbbVie, Falk, Gilead and Intercept. Thomas Reiberger: Grant support from Abbvie, Boehringer-Ingelheim, Gilead, Gore, Intercept, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, and Siemens; Speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; Consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; Travel support from Abbvie, Boehringer-Ingelheim, Gilead and Roche.

Clinical Case Summary

Colorectal lymphomas are a rare cause of colonic neoplasia (0.2-0.6% malignant neoplasms of large bowel). Approximately 10% are primary colorectal lymphomas, while the rest correspond to colonic extension of systemic lymphoproliferative diseases.
We present the case of a 66-year-old woman with a history of rectum and pancreas adenocarcinoma (both in remission). During a follow-up CT, a thickening of the cecal pole was identified, with no adenopathy or other relevant findings (Photo1). The patient had no abdominal pain or B symptoms (night sweats, weight loss or fever).
The diagnosis was completed with a PET-CT that showed pathological uptake in the cecum (Photo2), so a colonoscopy was performed, which revealed a large polypoid lesion (30 mm) at the ileocecal level, with nodular areas with small ulcerations and no clear loss of the glandular pattern (Photo 3), from which multiple biopsies were taken.
Biopsies showed lymphoid proliferation with a ‘starry sky’ pattern, mitosis and apoptosis, and positive immunohistochemistry for CD45, CD20, CD10, BCL6, BCL2 and C-MYC, together with a high proliferation index (Ki-67 > 95%), all compatible with high-grade B-lymphoproliferative syndrome with Burkitt morphology (Photo 4).
Burkitt's lymphoma is a rare B-cell lymphoma (15% of GI lymphomas), associated with chromosomal translocation (8:14, 8:22 and 2:8) and overexpression of c-myc oncogene.
There are three clinical variants: endemic (common in Africa and associated with EBV and malaria), HIV-associated and sporadic (20%).
It is common in children and its most frequent symptoms are abdominal pain and weight loss, so diagnosis is often delayed. Although the yield of endoscopic biopsies is low (<20%), it is a key tool in its diagnosis, along with targeted biopsy of abdominal adenopathies.
Despite its aggressiveness, treatment with targeted chemotherapy achieves rates of more than 90%, and early diagnosis is essential to avoid complications and ensure adequate medical treatment.

References

- Photo 1: Thickening of the cecal pole seen in CT-Scan.
- Photo 2: Pathological uptake in the caecal area as seen on PET-CT Scan.
- Photo 3: Polypoid lesion in ileocecal area at colonoscopy
- Photo 4: Pathological anatomy of endoscopic biopsies: starry sky imaging and immunohistochemistry of Bcl-2 and C-myc

Introduction

In the recent years, the therapeutic options for inflammatory bowel disease (IBD) have expanded. Multiple Janus kinase (JAK) inhibitors have been licensed: First Tofacitinib (TOFA) for Ulcerative Colitis (UC), followed, most recently, by Filgotinib (FIL) in UC and Upadacitinib (UPA) in UC and Crohn’s Disease (CD).

Aims & Methods

The aim of the study was to explore the real-world effectiveness and safety of UPA in a multicenter Belgium refractory cohort of patients with moderate-to-severe CD.
This is an observational, national, retrospective multicenter study including all patients with active CD initiating UPA between September 2022 and January 2024 from 16 Belgian centers. Clinical remission and response were defined using the two-component patient reported outcome. Endoscopic response was defined as a decrease in baseline Simple Endoscopic Score (SES-CD) with ≥ 50%. Endoscopic remission was defined as SES-CD ≤ 4 or disappearance of baseline ulcers. Effectiveness endpoints were evaluated at week 12, 24 and 52, while CD-related hospitalization, surgery and safety were assessed throughout follow-up.

Results

Of the 66 patients who started UPA, 52 patients were analysed (6 excluded for ostomy and 8 for not having yet reached 24 weeks of follow-up) with a median follow-up of 21 weeks (IQR: 4-24). Patients were predominately female (54%), median age at baseline was 37 years old (IQR: 19-62) and median disease duration was 13 years (IQR: 0-29). 12% of the patients had ileal CD, 12% colonic CD, 76% ileocolonic CD with 17% concomitant upper gastrointestinal CD and 42% concomitant perianal disease. The majority of the patients (87%) was exposed to ≥ 3 biologics and 54% had previously undergone a CD-related surgery.
At week 24, 58% and 44% of overall eligible patients achieved steroid-free clinical response and remission, respectively. Endoscopic data were available in 17 out of the 52 patients of whom 65% and 47% reached endoscopic response and remission respectively within the first 24 weeks. Sixteen out of eighteen patients that used concomitant steroids at baseline were able to stop it by week 24.
Overall, 21 patients (40%) discontinued their treatment during follow-up with a median exposure duration of 16 weeks (IQR: 4-24): 11 due to primary non response, 3 due to secondary loss of response, 7 due to adverse event (AE). Among these 21 patients, 4 patients underwent CD-related surgery (2 intestinal resections and 2 diverting ostomies) after a median duration of 15 weeks (IQR: 11-24), while the others switched to another medical therapy. In total, 21%% (11/52) patients required hospitalization within 24 weeks.
Twenty-seven AEs were reported in 19 (37%) patients, with 7 leading to treatment discontinuation (2 allergic skin rash, 1 severe acne, 1 folliculitis, 1 lip oedema, 1 severe stomatitis and 1 loss of appetite). The most common reported AEs were herpes simplex reactivation, respiratory tract infection, cutaneous reactions and acne. No herpes zoster infection, thrombotic or cardiovascular event were reported.

Conclusion

In this real-world cohort of highly refractory CD patients, UPA effectively induced steroid-free clinical remission and endoscopic remission by week 24 and was relatively well tolerated with respect to adverse events.

Disclosure

Dr Anneline Cremer has received lecture and advisory board fees from Galapagos, Abbvie, Janssen (2009-2014); lecture fees from Celltrion (2019-2024), Pfizer (2018-2023); advisory board fees from Takeda (2018-2023).
Dr Denis Franchimont has received lecture and/or advisory board fees from Abbvie, AstraZeneca, Dr. Falk Pharma, Ferring, Janssen, Mundipharma, MSD, Pfizer, Takeda, Amgen and research grants from Abbvie, Janssen, Takeda, Celltrion and Amgen (2019-2024).

Clinical Case Summary

Introduction: The most common complications of ERCP include acute pancreatitis, post-sphincterotomy bleeding, and intestinal perforation. Traumatic arterio-biliary fistulas, although rare, have been reported following manipulation. This case presents severe haemorrhage secondary to an arterio-biliary fistula.
Case Report: A 61-year-old male, chronic alcoholic with chronic liver disease (BCLC-B) and distal bile duct stricture of filarial aetiology, was admitted for biliary stent replacement. Post-procedure, the patient developed worsening clinical parameters, including abdominal pain, leucocytosis, and elevated cholestasis markers. Imaging revealed the proximal end of the stent was in the cystic duct, requiring a second ERCP for repositioning.
The patient's condition deteriorated with severe acute cholangitis, haemorrhagic rectal bleeding, and haemodynamic instability. CT showed further biliary dilatation and haematic content within the bile ducts. A third ERCP was performed to remove clots and place a covered metallic stent to control the bleeding. Despite this, haemorrhage persisted. CT-angiography revealed a 9 mm pseudoaneurysm from the pancreaticoduodenal arcade and pancreatic artery (Figure 1). Selective embolisation was successful (Figure 2), with follow-up confirming no further aneurysm filling (Figures 3 and 4).
Discussion: Arterio-biliary fistulas are typically iatrogenic or traumatic, often following biliary or hepatic procedures like liver biopsy or cholecystectomy. Post-ERCP incidence is rare, with only three reported cases. Diagnosis requires high clinical suspicion and angiography. Fistulas can cause pseudoaneurysms, which may lead to haemobilia, presenting as gastrointestinal bleeding. Management is multidisciplinary; conservative treatment is suitable for small, non-bleeding fistulas, while endoscopic or radiological interventions are used for severe cases. Early intervention is key to favourable outcomes.

References

1. Rai R. Potentially fatal haemobilia due to inappropriate use of an expanding biliary stent. World Journal of Gastroenterology. 2003;9(10):2377.
2. Berry R, Han J, Mohit Girotra, Tabibian JH. Hemobilia: Perspective and Role of the Advanced Endoscopist. 2018 Jul 12;2018:1–12.
3. Delayed Massive Hemobilia After Biliary Stenting. Endoscopy. 2003 Nov;35(11):976–7.
4. Siu, W. T., Chau, C. H., Ka Bo Law, B., Yau, K. K., Luk, Y. W., & KaWah Li, M. Non-operative management of endoscopic iatrogenic haemobilia: case report and review of literature. Acta gastro-enterologica Belgica. 2005;68(4): 428–431.
5. Panno, C., Gutiérrez, S. C., Echeverría, R., Garbe, C., Milocco, M., Ianniccillo, H., Valenzuela, M., Cubilla, A., Alvarez, F., & Alvarez, E. Hemobilia secundaria a pseudoaneurisma de la arteria hepática [Hemobilia secondary to hepatic artery pseudoaneurysm]. Acta gastroenterologica Latinoamericana. 2015;45(2):133–136.

Introduction

Currently, about 25-30% of the world population is affected by non-alcoholic fatty liver disease (NAFLD); over time, about 20% tends to develop a certain degree of inflammation in the liver tissue, defying the non-alcoholic steatohepatitis (NASH). Moreover, approximately 20% of NASH patients evolve into a high-grade liver fibrosis condition that leads to severe liver impairment (cirrhosis) (1, 2, 3).
The serial use of non-invasive fibrosis tests can refine prognosis in patients with non-alcoholic fatty liver disease (NAFLD) and evaluate the progression or improvement of liver fibrosis.

Aims & Methods

We evaluated predictors of improvement or worsening of liver stiffness measurements (LSM) in well characterized cohorts of patients with NAFLD from London (UK) and Milan (Italy).
We included two consecutive cohorts of 405 patients with at least two outpatient visits between 2014 and 2022. The minimum time interval between baseline and follow-up LSM was >6 months. LSM worsening was defined as an increase of >20% kPa if the baseline LSM was ≥5 kPa, or a follow-up LSM >6 kPa if the baseline LSM was <5 kPa. An LSM improvement was defined as an LSM decrease of >20% kPa (if the baseline LSM was >6 kPa).
A significant change in weight was defined as a >5% reduction or increase at follow-up, while a significant change in glycated hemoglobin (HbA1c) was defined as a >10% reduction or increase.
The variation between the true and expected FIB-4 index (based on the patient’s age at the follow-up visit, but using the blood tests performed at the first visit) was calculated. A significant improvement or worsening in FIB-4 was defined as a >20% variation between the actual and “expected” FIB-4.

Results

Of the 405 patients, 282 (70%) were males; mean age was 54±11 years. The median time from the first visits was 20.3 (13.9 – 28.7) months.
128 and 54 patients had an LSM >8 kPa and LSM>12 KPa at follow-up, respectively.
77 patients (19.3%) had an LSM improvement, while 67 (16.8%) had an LSM worsening; 256 patients (63.9%) maintained a stable value.
In patients with an LSM improvement, 22 had an improvement, 12 had worsening, while 37 had stable FIB-4.
In patients with an LSM worsening, 10 had an improvement, 20 had worsening, while 33 had a stable FIB-4.
In multiple logistic regression analysis, LSM worsening was independently associated with an increase in ALT and in HbA1c levels (OR 1.02 and 1.03 respectively), but also with a reduction in total cholesterol and AST levels (OR 0.98 for both). LSM improvement was independently associated with weight and ALT reduction (OR 0.93 and 0.98 respectively), but also with an increased AST level (OR 1.02).

Conclusion

More than 35% of patients with NAFLD have significant changes in their LSM measurements over a period of 20 months, with worsening or improvement at similar rates. Improvement in weight is independently associated with significant improvement in LSM measurements. On the converse, worsening in metabolic comorbidities, particularly glycemic control, could be associated with significant worsening in LSM, further supporting a multidisciplinary model of care.

References

1. Younossi Z, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018;15(1):11-20.
2. Sheka AC, et al. Nonalcoholic Steatohepatitis: A Review. JAMA 2020;323(12):1175-1183.
3. Liu J, et al. Estimating global prevalence, incidence, and outcomes of non-alcoholic fatty liver disease from 2000 to 2021: systematic review and meta-analysis. Chin Med J (Engl). 2022 Jul 20;135(14):1682-1691.