Clinical Case Summary

There is no clear consensus on the treatment of autoimmune hepatitis (AIH) with insufficient response to standard immunosuppressive therapy. ERN RARE-LIVER suggests infliximab as a third-line therapy. We report on a 35-year-old man diagnosed with AIH type 1 and and ulcerative pancolitis (UC) in 2006. AIH exhibited inadequate response to steroids and another immunosuppressive drugs (azathioprine, mycophenolate mofetil, tacrolimus). A liver biopsy in 2013 revealed severe activity and fibrous septa. Despite mild UC, infliximab was introduced in 2014 at 5 mg/kg every 4 weeks (then every 8 weeks) in conjunction with steroids and azathioprine (AZA), resulting in clinical and biochemical response in both diseases. By 2020, sustained biochemical response was achieved with infliximab, prednisone and AZA without infectious side effects. A liver biopsy in March 2023 revealed chronic hepatitis with no inflammatory activity and rare fibrous septa (METAVIR scoring system: activity grade 0, staging grade 2). Considering long-term risks of triple immunosuppression and the persistent remission of AIH and RCU, infliximab was discontinued in June 2023. Blood tests in October 2023 indicated a resurgence of transaminases (ASTx12,6, ALTx19,7 ULN) and IgG (x2,1 ULN), rise in bilirubin (total/conjugated 2,83/1,40 mg/dl). Patient was hospitalized, intravenous methylprednisolone was administered with mild decrease in liver tests. Considering that AIH flare, infliximab was reintroduced in November 2023 together with prednisone and AZA. Blood tests after 2 weeks showed AST normalization, ALT x1,3 and IgG x1,2 ULN, bilirubin total/conjugated 1,89/0,36 mg/dl. No adverse events were experienced. Our case underscores that in rare instances, AIH may necessitate triple combination therapy to induce and maintain remission, including infliximab. Given the possible long-term risks of this level of immunosuppression, it is mandatory to carefully evaluate such patients in a case-by-case manner.

References

AW Lohse, M Sebode, MH Jørgensen et al. Second-line and third-line therapy for autoimmune hepatitis: A position statement from the European Reference Network on Hepatological Diseases and the International Autoimmune Hepatitis Group. Journal of Hepatology 2020 vol. 73, 1496-1506

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is recognized as a foundational procedure within the realm of interventional gastroenterology. Nevertheless, a significant amount of hands-on experience is required to achieve proficiency in this procedure, particularly with regard to the performance of sophisticated therapeutic maneuvers. Access to authentic training cases remains limited, while the use of cadaveric or live animal models presents distinct ethical, logistical and financial challenges (1). The advent of 3D printing technology paved the way for the development of advanced medical simulators. This study utilized computer-aided design and fused deposition modeling techniques to engineer an ERCP simulator that is both anatomically accurate and enables the training of trainee physicians in the intricate procedures of their chosen discipline (2). The simulator's modular design allows it to replicate a spectrum of papillary conditions, enabling targeted training in anatomies that are resistant to cannulation, as well as high-risk procedures like precut sphincterotomy and fistulotomy.

Aims & Methods

The design process for the ERCP simulator employed accessible parametric modeling software. Fabrication of the primary structural components, including the pancreas, the duodenum, and the bile ducts, were undertaken using polylactic acid (PLA) filament, a material that is both widely accessible and economical, thereby ensuring adequate rigidity and durability. The interchangeable papillary components were produced using flexible thermoplastic polyurethane (TPU) 95A filament, selected for its elasticity and capacity to be readily incised during procedures such as endoscopic sphincterotomy (EST). This allowed for easy exchangeability and facilitated the acquisition of skills by novice endoscopists. This process were selected on the basis of accessibility, user-friendly interface and cost-effectiveness, enabling replication in diverse settings. The biliary and pancreatic ductal lumens were meticulously calibrated to represent a range of procedural difficulty, with internal diameters that closely mirrored real anatomical variations.

Results

The simulator exhibited a high degree of anatomical and biomechanical fidelity, featuring a structurally stable duodenal framework and a flexible papillary interface. The simulator accurately reproduced tactile feedback experienced by gastroenterologists during ERCP, thereby validating its efficacy as a training tool. Furthermore, the simulator was enabled meticulous rehearsal of EST through sphincterotomy incisions and facilitated fistulotomy simulation using an elastomeric papilla structure. The simulator's design is both cost-effective and easily replicable, making it a valuable asset for continuing education and training in this field (3,4).

Conclusion

The ERCP simulator, fabricated using 3D printing technology, can be regarded as both technologically advanced and economically efficient for a number of complex procedures. These encompass endoscopic sphincterotomy, precut techniques, fistulotomy and stent placement. The simulator's design, featuring a modular papillary system, was crafted to provide a structured and progressive learning environment for novice users as well as experienced endoscopists. The simulator's cost-effectiveness, ease of scaling up and potential for wide dissemination signify a paradigm shift in ERCP education, facilitating proficiency acquisition in complex interventional endoscopy with greater efficiency and safety. Further investigations are needed for the simulator in ERCP training.

References

1. Lee S, Ahn JY, Han M, Lee GH, Na HK, Jung KW, et al. Efficacy of a three-dimensional-printed training simulator for endoscopic biopsy in the stomach. Gut and liver. 2017;12(2):149.
2. Zhang Y, Chen L, Hu B. Advances of 3D printing in gastroenterology and where it might be going. International Journal of Bioprinting. 2023;9(6):0149.
3. Lee DS, Ahn JY, Lee GH. A newly designed 3-dimensional printer-based gastric hemostasis simulator with two modules for endoscopic trainees (with video). Gut and Liver. 2019;13(4):415.
4. Bundy JJ, Weadock WJ, Chick JFB, Srinivasa RN, Patel N, Johnson E, et al. Three-dimensional printing facilitates creation of a biliary endoscopy phantom for interventional radiology-operated endoscopy training. Current Problems in Diagnostic Radiology. 2019;48(5):456-61.

Clinical Case Summary

Introduction: Wilson’s disease is a rare inherited liver disorder caused by copper metabolism dysfunction,whereas Crohn’s disease is a chronic inflammatory bowel condition.The co-occurrence of both conditions in an adolescent is extremely rare and becomes particularly noteworthy when associated with severe complications.
Case presentation: We report a 17-year-old male with cirrhotic Wilson’s disease,stable on D-penicillamine, who developed severe anal pain and bloody diarrhea.On proctologic examination,he had hemorrhoids, a s crotal fissure,and a non-draining anal fistula.
Laboratory investigations revealed severe anemia (Hb 4.4 g/dL),leukopenia,and elevated C-reactive protein. Colonoscopy showed multiple ileocolic ulcers on edematous mucosa, suggestive of active Crohn’s disease, confirmed by histopathological examination of biopsies. Pelvic MRI identified a grade II active, intersphincteric, abscessed perianal fistula. Antibiotic therapy was initiated accordingly. The patient was treated with high-dose intravenous corticosteroids for three weeks, followed by oral tapering, leading to significant clinical and laboratory improvement. However, during hospitalization, he developed disseminated intravascular coagulation (DIC) with thrombotic microangiopathy, requiring transfusion of fresh frozen plasma.His condition improved favorably thereafter
Discussion: The coexistence of Wilson’s and Crohn’s diseases is extremely rare. This case stands out for the onset of severe Crohn’s in a patient with chronic liver disease, a complex perianal fistula needing multidisciplinary care,and DIC with thrombotic microangiopathy—likely from systemic inflammation. It highlights the diagnostic and therapeutic challenges in adolescents with multiple chronic illnesses

Conclusion: The association between Wilson’s disease and Crohn’s disease is exceedingly rare. This case emphasizes the need for a multidisciplinary approach in managing complex patients, particularly when faced with severe complications.

Clinical Case Summary

Hydatid cyst disease, caused by the Echinococcus parasite, is a zoonotic infection that typically targets the liver, lungs, and nervous system. It commonly occurs in regions such as the Maghreb countries, where it presents a significant health concern. While hydatid cysts in the liver are usually asymptomatic, complications such as cyst rupture, infection, or obstruction can arise, with portal vein involvement being particularly rare. This case report describes a 56-year-old male with a history of surgery for hydatid liver cyst, who presented with portal vein invasion mimicking portal vein thrombosis. Diagnostic imaging, including Color Doppler ultrasound and MRI, revealed a multiloculated cyst in the fourth liver segment with communication to the portal vein, leading to thrombosis and cavernous transformation of the portal vein. Despite the rupture of the hydatid cyst into the portal vein, no anaphylactic shock occurred. Portal vein thrombosis and cavernous transformation due to hydatid cysts represent an exceptional and complex complication of echinococcosis, highlighting the importance of early recognition and appropriate management. Treatment strategies should address both the hydatid liver cyst and associated portal hypertension, with surgical intervention being the cornerstone, including hepatectomies and laparoscopic approaches. This case highlights the necessity of heightened clinical awareness in endemic regions for managing this rare, potentially life-threatening complication.

Introduction

Alkaline phosphatase (ALP) is an important marker in primary biliary cholangitis (PBC) associated with risk for disease progression. In the pivotal, Phase 3, placebo-controlled RESPONSE trial (NCT04620733), seladelpar, a first-in-class delpar (selective PPAR-delta agonist), led to a significantly higher percentage of PBC patients achieving the composite biochemical endpoint (ALP <1.67 x upper limit of normal [ULN], ALP decrease ≥15%, and total bilirubin [TB] ≤ULN) compared with placebo (61.7% vs 20%) and decreased mean ALP levels after one year (-42.4% vs -4.3%, respectively). Here, we report additional data on ALP changes in the RESPONSE trial.

Aims & Methods

PBC patients who received ursodeoxycholic acid (UDCA) for ≥12 months or were UDCA intolerant and had ALP ≥1.67 x ULN and TB ≤2 x ULN were randomised 2:1 to daily seladelpar 10 mg or placebo. We assessed ALP changes across demographic subgroups, baseline ALP quartiles, and in patients who did not meet the composite biochemical endpoint. Worsening of ALP (increase >0 U/L from baseline) and safety by baseline ALP subgroup were also evaluated.

Results

128 patients were randomised to seladelpar and 65 to placebo with mean baseline ALP 314.6 U/L and 313.8 U/L, respectively; 53 (27.5%) patients had baseline ALP ≥350 U/L. Seladelpar reduced ALP at month 12 similarly across all subgroups, including in patients with cirrhosis, aged <50 years at PBC diagnosis, and of Hispanic/Latino ethnicity, vs placebo. For patients with baseline ALP ≥350 U/L, seladelpar led to a greater decrease (-44.8%; -216.1 U/L) in ALP vs placebo (-11.6%; -56.4 U/L); similar percent decreases were seen in patients with baseline ALP <350 U/L. Seladelpar reduced ALP similarly across baseline ALP quartiles. Among patients who did not meet the composite biochemical endpoint at month 12, ALP was decreased by -129.9 U/L for seladelpar vs -6.4 U/L for placebo. Seladelpar prevented worsening of ALP, with 7 (5.5%) seladelpar patients vs 19 (29.2%) placebo with increases in ALP from baseline at month 12. Adverse events were reported in 86.4% of patients with baseline ALP <350 U/L and 84.9% of patients with ALP ≥350 U/L, with similar proportions in seladelpar vs placebo patients.

Conclusion

Seladelpar led to robust and consistent ALP decreases across all subgroups studied. Substantial ALP decreases were also observed in patients who did not meet the composite endpoint criteria at month 12. Seladelpar was overall safe and well tolerated, regardless of baseline ALP level.

Disclosure

KVK reports receiving grants or contracts from 89Bio; Boston Scientific; Corcept Therapeutics; CymaBay Therapeutics; Genfit; Gilead Sciences, Inc.; GSK; Hanmi Pharmaceuticals; Intercept Pharmaceuticals; Ipsen; Janssen; Madrigal Pharmaceuticals; Mirum Pharma; NGM Bio; Novo Nordisk; Pfizer; Pliant Therapeutics; Terns Pharmaceuticals; Viking Therapeutics; and Zydus Pharmaceuticals; royalties or licences from UpToDate; consulting fees from 89Bio; CymaBay Therapeutics; Genfit; Gilead Sciences, Inc.; GSK; HighTide Biopharma; Inipharm; Intercept Pharmaceuticals; Ipsen; Madrigal Pharmaceuticals; Mirum Pharma; NGM Bio; and Zydus Pharmaceuticals; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie; Gilead Sciences, Inc.; and Intercept Pharmaceuticals; participation on a data safety monitoring board or advisory board with CTI and Medpace; and stock or stock options with Inipharm. KKY reports receiving honoraria from Gilead Sciences, Inc. SK reports receiving grants or contracts from Gilead Sciences, Inc.; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead Sciences, Inc. EM reports receiving payment or honoraria for speakers bureaus from AbbVie; Eli Lilly; Gilead Sciences, Inc.; and Ipsen; and support for attending advisory boards from AbbVie; Eli Lilly; Gilead Sciences, Inc.; and Ipsen. AB reports receiving grants or contracts and consulting fees from Chemomab; CymaBay Therapeutics; Gilead Sciences, Inc.; GSK; Intercept Pharmaceuticals; Ipsen; and Mirum Pharma; royalties or licences from UpToDate; payment for expert testimony from UMass; and participation on a data safety monitoring board or advisory board with Pfizer. KGR reports receiving grants or contracts from COUR Pharmaceuticals; CymaBay Therapeutics; Gilead Sciences, Inc.; and Pliant Therapeutics; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Mallinckrodt Pharmaceuticals and Gilead Sciences, Inc. CC reports consulting for CymaBay Therapeutics and Ipsen. JMS reports consultant honoraria from 89Bio; Alentis; Alexion; Altimmune; AstraZeneca; Bionorica; Boehringer Ingelheim; Gilead Sciences, Inc.; GSK; Inventiva Pharma; Ipsen; Lilly; Madrigal Pharmaceuticals; MSD; NorthSea Therapeutics; Novartis; Novo Nordisk; Pfizer; Roche; Sanofi; and Siemens Healthineers; speaker honoraria from AbbVie; Boehringer Ingelheim; Echosens; Gilead Sciences, Inc.; Madrigal Pharmaceuticals; Medscape; and Novo Nordisk; and stockholder options with AGED Diagnostics and Hepta Bio. SC, KY, and DBC are employees of Gilead Sciences, Inc., and may own stock in Gilead Sciences, Inc. CAM reports former employment with CymaBay Therapeutics, a Gilead Sciences, Inc., company, from 2007 to 2024; receiving consulting fees from Gilead Sciences, Inc.; being listed as an inventor on seladelpar patents; and a leadership or fiduciary role (paid or unpaid) with 89Bio (independent director).

Clinical Case Summary

Drug-induced liver injury is an adverse effect of many pharmaceutical agents. Alverine citrate, an antispasmodic agent found in the fixed-dose combination Meteospasmyl (alverine citrate and simethicone), is widely used in functional gastrointestinal disorders. To date, only three cases are published in the literature. We report a case, with strong evidence, including a rechallenge confirming the causality.
Patient Observation: A 43-year-old woman presented with biliary-type abdominal pain. Her medical history was limited to hypertension treated with bisoprolol with no alcohol use or recent medication. Abdominal ultrasound revealed uncomplicated cholelithiasis; liver tests were normal. Alverine citrate was prescribed for symptomatic relief. Within two weeks, she developed jaundice and fatigue with a normal clinical examination. Blood tests showed severe hepatocellular injury: ALT and AST were 22× and 39× ULN, bilirubin was 274 µmol/L, and GGT/ALP were mildly elevated. Viral and autoimmune panels were negative. Imaging excluded biliary obstruction. Liver biopsy revealed portal inflammation with eosinophilic infiltrates, suggestive of immunoallergic hepatitis. The discontinuation of the drug led to normalization of liver enzymes. 3 years later, the patient was inadvertently re-exposed to alverine citrate, triggering a reproducible episode of acute hepatitis, thereby confirming causality. Diagnostic probability was assessed with the RUCAM score (12, "highly probable") and Naranjo scale (8, "probable"). Only three prior cases of alverine citrate-induced hepatitis, none of which reported a confirmed rechallenge. Although liver biopsy is not routinely required in DILI, it was essential here for diagnostic clarification.
Alverine citrate should be recognized as a rare cause of acute hepatitis. This case confirms its hepatotoxic potential and underscores the importance of early recognition and drug withdrawal to prevent recurrence.

References

1. RUCAM Scale: https://clincasequest.hospital/rucam-scale/
2. Naranjo Scale: https://proeurodilinet.eu/wp-content/uploads/2019/03/Causality-assessment-training-course-15-MARCH-.pdf
3. Couzigou P et al. Hepatitis and Alverine Citrate. J Hepatol. 1997. https://www.sciencedirect.com/science/article/abs/pii/S0168827897801870
4. Turkish case report. Turk J Gastroenterol. 2004. https://pubmed.ncbi.nlm.nih.gov/15259090/
5. Korean case report. Korean J Hepatol. 2010. https://pubmed.ncbi.nlm.nih.gov/20375645/
6. Simethicone safety review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033443/
7. Zhang X et al. Histopathologic Manifestations of Drug-induced Hepatotoxicity. Clin Liver Dis. 2013.

Introduction

The effectiveness of anti-Helicobacter pylori treatment decreases as therapy failure accumulates. Different consensuses recommend knowing the regional performance of therapeutic regimens to achieve better eradication results in real clinical practice.

Aims & Methods

To evaluate the effectiveness of empirical therapy in second and subsequent treatment lines in Brazil.
Real-life, multicenter, prospective, non-interventional registry evaluating outcomes of H. pylori management by Brazilian gastroenterologists (Hp-BrazilReg, WorldHpReg’s partner). Data were registered at e-CRF AEG-RedCap from March 2022 to October 2024. The effectiveness was evaluated by modified intention-to-treat (mITT) analysis. Data were subject to quality review.

Results

​572 patients, with a mean age of 52 years, 64% women, were evaluated. The main treatment indications were dyspepsia (64%) and gastroduodenal ulcer (9.2%). 386 (67%) patients received a second-line therapy, and 186 (32%) received third-line or subsequent therapy. Low-dose (between 4.5 and 27 mg of omeprazole equivalent BID), standard-dose (between 32 and 40 mg of omeprazole equivalent BID), and high-dose (between 54 and 128 mg of omeprazole BID) proton pump inhibitor (PPIs) were used in 40%, 10%, and 24%, respectively. Vonoprazan (VPZ) 20 mg BID, was used in 26% of cases. With the second-line treatment, the overall eradication rate was 74%. The most frequently used regimen was the triple therapy with PPI+amoxicillin+levofloxacin for 10-14 days, in 55% of the patients. This regimen, recommended as an alternative by the Brazilian Consensus, achieved an eradication rate of 84% (14 days) and 55% (10 days). By adding bismuth to this same 14-day regimen the effectiveness increased to 100% (p=0.016). Regarding the third-line, the regimen containing PPI-bismuth-tetracycline-metronidazole was used in 24% of the cases, achieving 87% mITT cure rate. Within the fourth-line, dual therapy including amoxicillin-VPZ was the most common regimen (33%), achieving 100% eradication, followed by bismuth quadruple therapy with PPI+bismuth+amoxicillin+rifabutin (14%), showing 100% effectiveness. Dual therapy with VPZ+amoxicillin was also the most used regimen in the fifth-line and subsequent treatment lines, encompassing 43% of the cases, and achieving also 100% effectiveness. Overall, 23% of the patients presented mild adverse events being nausea the most frequent (14%), and compliance was 99%.

Conclusion

In Brazil, the overall effectiveness of second-line therapy showed suboptimal (≤90%) cure rate; however, the combination of bismuth-amoxicillin-levofloxacin prescribed for 14 days reported successful effectiveness. In the third-line, the classical bismuth-quadruple therapy with metronidazole-tetracycline provided encouraging results (87%). Alternatively, dual therapy with VPZ and amoxicillin and rifabutin-based bismuth quadruple therapy showed promising results in third- and fifth-line rescue treatment.