Introduction

Limited knowledge regarding vitamin A deficiency in cancer patients is available. Vitamin A is a fat-soluble vitamin crucial for cell development, immune competency, metabolism and vision. Absorption of vitamin A in the proximal parts of the small intestine follows its hydrolyzation by pancreatic and intestinal enzymes and emulsification by bile acids. Xerophthalmia and incipient night blindness can serve as clinical reminder of vitamin A deficiency and can be a reversable phenomenon. The aim of our study was to establish the incidence of vitamin A deficiency in patients suffering from bile acid malabsorption (BAM) and/or syndrome of intestinal bacterial overgrowth (SIBO) and/or exocrine pancreatic insufficiency (EPI) as a consequence of cancer treatment.

Aims & Methods

This was a retrospective evaluation of data in individuals reviewed within twelve months period (January 2022 - December 2022) in a specialized gastroenterology clinic in a tertiary centre. Patients who had undergone any anti-cancer treatment (chemotherapy and/or radiotherapy/and or surgery) and have been suffering from gastrointestinal (GI) symptoms are referred to this clinic. The electronic patient records system was searched. Demographic data, incidence of BAM (assessed with SeHCAT scan: retention on day 7 <20%) and/or SIBO (evaluated by glucose breath test – positivity in production of hydrogen and/or methane) and/or EPI (based on investigation of faecal elastase: <200ug/g) and serum vitamin A levels (normal ranges: 1.07-3.55 µmol/L) were assessed. In one patient who could not have the above investigations due to severity of symptoms, therapeutic trial resulting in clear response to medication (Rifaximin / pancreatic enzymes) was used for the diagnosis of SIBO or EPI. The study was approved by CCR committee (reference number: SE 1267

Results

A total of 453 consecutive patients were seen. Out of 453 patients, 23% (101/453) were diagnosed with BAM, 4% (17/453) with BAM and SIBO, 3% (14/453) with BAM and EPI, 3% (15/453) were diagnosed with SIBO, 3% (12/453) with EPI and 2% (10/453) with SIBO and EPI. Out of 169 patients (169/453; 37%) who suffered from BAM and/or SIBO and/or EPI, five patients (3%; 5/169) were diagnosed with serum vitamin A deficiency. Three of them (2%; 3/169) received oral supplementation (those were diagnosed with BAM+EPI, SIBO+EPI and isolated EPI) and two (1%; 2/169) required intramuscular supplementation due to a significantly impaired vision, mainly night blindness and a very low serum vitamin A level (0.11 µmol/L; 0.25 µmol/L). The first patient (diagnosed with SIBO in combination with EPI) received three doses of vitamin A 100.000 IU and another ten doses of 50.000 IU intramuscularly. The second patient (diagnosed with BAM) received a single dose of vitamin A 100.000 IU and four doses of 50.000 IU intramuscularly. In the first patient who had a more prolonged history of nutritional deficiency as well as possible additional as yet undiagnosed cause for the retinal dysfunction, vision improved but the patient continued to have reduced visual function. In the other patient the vision returned to normal. The most recent serum vitamin A levels have been 1.73 µmol/L and 1.76 µmol/L.

Conclusion

Incidence of vitamin A deficiency in a cohort of patients who underwent treatment for cancer and developed GI consequences was 3%, however it can be severe, with significant clinical consequences. Timely recognized severe vitamin A deficiency can be reversible if an appropriate parenteral supplementation is administered.

Disclosure

No conflict of interest

Clinical Case Summary

A 22-year-old female without comorbidities presented with epigastric and lower retroesternal chest pain, nausea and vomiting since 3 days that didn't response to oral medication. Patient denied dysphagia or odinophagia. Assessed in the emergency, treated with intravenous (IV) medications and discharged with prescription. Next day, the pain increased and vomited 15 times. Patient was admitted as a case of acute gastritis on intravenous proton pump inhibitors (PPIs) and metoclopramide. Routine laboratory and upper abdominal ultrasound done without significant findings only remarkable mild hyponatremia 134 (135-145).
Physical examination looked unwell. Vitally stable 105/75 mmHg. Afebrile (36.2). Malnourished. Weight 28.7 Height 145cms BMI 14.2. Mild epigastric tenderness.
Due to refractory symptoms despite IV medication. Endoscopy was done and showed round and serpiginous ulcers in the lower third of the esophagus with yellowish exudate suggestive of infectious esophagitis Cytomegalovirus vs Herpes. Normal aspect of stomach and duodenum. Histopathology confirmed herpes simplex esophagitis.
Under the suspicion of infectious esophagitis HIV serology came negative, CMV antibodies IgM negative IgG positive. Normal immunoelectrophoresis. No previous herpes viral infection. The only risk factor identified for the patient was the malnutrition, nevertheless vitamins and proteins were normal.
With histological confirmation after 48 hours of the endoscopy she was started on Acyclovir IV 5mg/kg every 8 hours with significant improvement in the next 48 hours. Patient discharged in stable condition after re-starting oral intake and completing the oral acyclovir 400 mg every 8 hours for 10 days. Patient responded well was assessed 7 days after discharge, free of symptoms and a weight gain of 1.3 kg.
Infectious esophagitis needs to be considered in immunocompetent host. Odynophagia/dysphagia can be absent. Endoscopy findings alone isn't sufficient to make a definitive diagnosis.

References

Endoscopy and histopathology.

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.

Introduction

There is an unmet need for adjunctive therapies for patients with celiac disease (CeD) who experience inadequate disease control while maintaining a gluten-free diet (GFD). The optimal trial design to assess CeD treatment efficacy is unclear and increased adherence to a GFD during trials may improve disease control. We assessed symptom severity changes during the screening and run-in periods (no treatment) of two phase 2b CeD trials, one using simulated inadvertent gluten exposure (SIGE) and one without.

Aims & Methods

In two concurrent ongoing phase 2 CeD trials (NCT05353985 and EudraCT2020-004612-97) daily gastrointestinal (GI) symptom severity was measured using the Celiac Disease Symptom Diary 2.1^© during the screening and run-in periods (4 weeks each in NCT05353985; 6 weeks and 5 weeks, respectively in EudraCT2020-004612-97) before any treatment administration. In both trials, eligible patients had biopsy-confirmed CeD and were experiencing CeD-related symptoms and enteropathy despite following a GFD. NCT05353985 included food bars containing ~500 mg gluten, consumed 3-times weekly after Week 2, for 2 weeks during the run-in period (post randomization). EudraCT2020-004612-97 did not include gluten exposure. Mean GI symptom severity scores were calculated each week during the screening and run-in periods.

Results

From the start of the screening period through to the end of the run-in period, mean GI symptom severity scores improved significantly in EudraCT2020-004612-97 (0.96 at Week 1 of screening, and 0.75 at Week 5 of run-in) whereas changes were non-significant in NCT05353985 (0.96 at Week 1 of screening and 0.92 at Week 4 of run-in).

Conclusion

Clinical trial participation may result in an improvement in CeD-related GI symptoms due to better GFD adherence. Administration of SIGE can minimize such trial effects and does not worsen symptoms in patients with CeD.

Disclosure

SB, NC, AH, DAL and QL are employees and shareholders of Takeda.
KH RM and RM are employees of Dr. Falk Pharma GmbH.
JM reports grants (to institution) from, National Institutes of Health, Immunogenix, Takeda Pharmaceutical, Allakos, ProventionBio, Oberkotter Foundation, and 9Meters, Inc.; contract (to institution) from Kanyos Bio (a wholly owned subsidiary of Anokion); and consultancy fees from Johnson and Johnson, Bristol Myers Squibb, Intrexon Corporation, Dren Bio, Neoleukin, Reistone pharma, GSK, Immunic Therapeutics, Brightseed Bio, Chugai Pharma, Alimentiv, Equillium, Ukko, Medibeacon, Israel Biotech Fund, Precigen, triangle insights group, Sanofi, Zag Bio, Loop bio and Orbimed; and has received royalties from Evelo. MS has no funding to disclose relating to this study and is the Principal Investigator in the EudraCT2020-004612-97 clinical trial.
MS has no funding to disclose relating to this study and is the Principal Investigator in the EudraCT2020-004612-97 clinical trial.
ML receives research funding from Takeda and Moderna, and has previously acted as a consultant for Anokion and Amgen.
JS reports grants (to institution) from Celiac Disease Foundation, National Institutes of Health, Takeda Pharmaceutical, Allan Foundation and consultancy fees from Alimentiv and Takeda Pharmaceuticals.
DS received study related management/advisory fees from Dr. Falk Pharma.

Introduction

People who use drugs (PWUD) are an important target population for hepatitis C virus (HCV) elimination in the World Health Organization (WHO) goals, because the PWUD population contains one of the largest clusters of residual HCV infections. Case-finding and treatment of these patients in hospitals is considered a challenge, while low threshold on-site screening and therapy in addiction care might facilitate viral elimination. We studied implementation of a decentralized PWUD-HCV care model, by exploring 1) viral elimination rates, and 2) facilitators and barriers for implementation.

Aims & Methods

In a multicenter mixed-method study in addiction care centers in the Netherlands we examined HCV-related outcomes in PWUD receiving HCV treatment within addiction care. The primary outcome was viral elimination, defined as percentage of identified HCV positive patients achieving sustained virologic response (SVR). Using semi-structured interviews barriers and facilitators for implementation were identified among health professionals and policy makers of addiction care and hospitals.

Results

We found 33 PWUD HCV RNA positive. Four patients were referred to the hospital for treatment due to hepatitis B virus or HIV co-infection or other reasons. Two patients currently receive treatment, three patients were not yet fit for treatment and two were lost to follow-up before treatment could be started. On-site treatment was initiated in 22 patients. Of these patients 91% was male, mean age was 50 years (SD=13) and 36% was born in the Netherlands. All patients completed treatment with glecaprevir/pibrentasvir (n=9) or sofosbuvir/velpatasvir (n=13). All on-site and hospital treated patients reached SVR and there were no reinfections. The viral elimination rate was 79% (26/33). Themes on facilitators and barriers for implementation collected in the interviews are shown in the table.

Conclusion

This study shows the high viral elimination (79%) of decentralized care of HCV infections within addiction care and provides insight in facilitators and barriers for on-site HCV treatment. Based on these findings we recommend implementation and maintenance of decentralized HCV-addiction care models worldwide. This will lead to HCV elimination scaling-up in the Netherlands and abroad, furthering WHO goals.

References

Madden, A., Hopwood, M., Neale, J., & Treloar, C. (2018). Beyond interferon side effects: What residual barriers exist to DAA hepatitis C treatment for people who inject drugs? PLoS One, 13(11), e0207226. https://doi.org/10.1371/journal.pone.0207226
Oru, E., Trickey, A., Shirali, R., Kanters, S., & Easterbrook, P. (2021). Decentralisation, integration, and task-shifting in hepatitis C virus infection testing and treatment: a global systematic review and meta-analysis. The Lancet Global Health, 9(4), e431-e445. https://doi.org/10.1016/s2214-109x(20)30505-2
Von den Hoff, D. W., Berden, F. A. C., Atsma, F., Schellekens, A. F. A., & Drenth, J. P. H. (2022). Against All Odds? Addiction History Associated with Better Viral Hepatitis Care: A Dutch Nationwide Claims Data Study. J Clin Med, 11(4). https://doi.org/10.3390/jcm11041146
European Association for the Study of the Liver, e. e. e., Clinical Practice Guidelines Panel, C., representative, E. G. B., & Panel, m. (2020). EASL recommendations on treatment of hepatitis C: Final update of the series(). J Hepatol, 73(5), 1170-1218. https://doi.org/10.1016/j.jhep.2020.08.018

Disclosure

Daan Von den Hoff and Joost Drenth declare receipt of funds from Abbvie and Gilead; the other authors have nothing to declare.

Introduction

Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative strategy for chronic hepatitis B (CHB), but data on optimal biomarkers for post-treatment monitoring is limited.

Aims & Methods

With the aim to investigate whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR), this retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase (ALT) > 80 U/L with recurrent viremia. During follow-up, serum HBcrAg was evaluated as a time-varying variable in the Cox proportional hazard model.

Results

The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.1% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1% ‐ 62.4%). Time-varying HBcrAg levels were a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.43 per log U/mL; 95% CI, 1.16-1.76) in the multivariable model adjusted for EOT HBsAg level, anti-HBe antibody, and EOT ALT. During follow-up, HBcrAg < 1,000 U/mL predicted a low risk of subsequent CR (aHR, 0.31; 95% CI, 0.17-0.57).

Conclusion

Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be used to guide posttreatment monitoring.

References

1. Mak LY, Wong DK, Cheung KS, Seto WK, Lai CL, Yuen MF. Review article: Hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther. 2018;47(1):43-54.
2. Hsu YC, Nguyen MH, Mo LR, Wu MS, Yang TH, Chen CC, et al. Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk. Aliment Pharmacol Ther. 2019;49(1):107-15.
3. Sonneveld MJ, Park JY, Kaewdech A, Seto WK, Tanaka Y, Carey I, et al. CREATE Study Group. Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE). Clin Gastroenterol Hepatol. 2022 Apr;20(4):e784-e793

Introduction

Intestinal point-of-care ultrasound, as standardized by the International Bowel Ultrasound Group (IBUS), has emerged as a valuable tool for diagnosing, monitoring, and managing patients with Inflammatory Bowel Disease (IBD). While IBUS emphasizes a structured intestinal assessment, some European centers adopt a more comprehensive approach, combining intestinal ultrasound with a complete abdominal examination.
The Karolinska Centre for Digestive Health, a tertiary referral institution providing specialized care to approximately 4,500 patients with IBD, established a dedicated Gastrointestinal Ultrasound Unit in October 2023. This unit offers advanced diagnostic services to both hospitalized patients and those treated on an outpatient basis.

Aims & Methods

This retrospective study aimed to assess the prevalence of secondary extraintestinal findings in IBD patients undergoing comprehensive abdominal ultrasound between October 4, 2023, and March 4, 2025. All patients underwent ultrasound assessments that included both intestinal and abdominal imaging. Patients referred for indications unrelated to intestinal ultrasound (IUS), as well as those undergoing repeat examinations, were excluded from the analysis to ensure data consistency.
All examinations were performed by a single gastroenterologist with 25 years of ultrasound experience. In cases where secondary extraintestinal findings were identified, patients’ electronic medical records were reviewed to determine whether these findings represented new diagnoses or previously known conditions.

Results

The study included 348 patients with IBD, 201 (58%) females and 147 (42%) males, with a mean age of 42.4 years. Among these, 260 (75%) were referred internally by our IBD Outpatient Clinic, 47 (13%) by the Gastroenterology Ward, 33 (10%) by private outpatient clinics, and the remainder from other healthcare sites. IUS revealed evidence of intestinal inflammation in 144 patients (42%), while findings were normal in 204 patients (58%).
Furthermore, 150 patients presented with a total of 195 secondary extraintestinal findings, of which 113 (58%) represented newly identified pathologies. Among all secondary findings, the majority, 104 (53%), were related to the hepatobiliary system, including 33 newly diagnosed cases of hepatic steatosis and 17 new cases of cholecystolithiasis. One patient demonstrated ultrasound features suggestive of primary sclerosing cholangitis (PSC) and is currently undergoing further evaluation. Additional findings involved the reproductive system (29/15%), urinary system (15/7%), spleen (32/16%), and pancreas (5/2%). Various other intra-abdominal findings were also identified (37/18%). Notably, one patient presented with a suspicious mass in the right iliac fossa, and another demonstrated ultrasound findings suggestive of a prostatic tumor; both cases were referred for further oncologic evaluation. Additionally, three patients were newly diagnosed with intraductal papillary mucinous neoplasm (IPMN), which was subsequently confirmed via magnetic resonance imaging, and all were enrolled in the national IPMN surveillance protocol.

Conclusion

A considerable proportion of patients with IBD were found to have previously unknown extraintestinal abdominal pathologies, underscoring the essential role of comprehensive ultrasound examination that combines both intestinal and abdominal assessment. Fortunately, only a minority of these findings resulted in changes to patient management.

Disclosure

Francesca Bresso has acted as national and/or local principal investigator for clinical trials for Janssen, Ferring, and AbbVie. Charlotte Hedin served as a speaker and/or advisory board member for AstraZeneca, AbbVie, Dr. Falk Pharma and the Falk Foundation, Galapagos, Janssen, Pfizer, Ferring, Takeda, and Tillotts Pharma and received grant support from Tillotts Pharma and Takeda. Stephan L. Haas has served as a speaker for Takeda, Santax Medico, Tillotts Pharma, Johnson & Johnson, and Mediahuset. The rest of the authors have nothing to declare.