Introduction

Helicobacter pylori treatment´s effectiveness decreases as treatment eradication attempts fail.

Aims & Methods

To evaluate the use and effectiveness of empirical rescue therapies on third and subsequent lines, in Europe.
Sub-study of the the European Registry on H. pylori Management (Hp-EuReg), an international, multicenter, prospective, non-interventionist registry starting in 2013 aiming to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists (38 countries, 400 researchers). All infected adult patients were systematically registered at AEG-REDCap e-CRF until December 2023, all cases with three or more eradication attempts were extracted. Only the empirically prescribed therapies were considered. Effectiveness was analysed by modified intention-to-treat (mITT) and per protocol (PP). Data were subject to quality review.

Results

In total, 3,351 rescue treatments were included: 2,349, 688, 228 and 86 in third-, fourth-, fifth- and sixth-line treatments, respectively. Mean age was 51 years, 68% of patients were women and 5.3% were allergic to penicillin. Sixty-eight different treatment schemes were used, being the three-in-one single-capsule bismuth quadruple therapy the most commonly prescribed (Table). Overall effectiveness was 73% by mITT, and 74% by PP analyses. Bismuth quadruple therapy as single-capsule provided the highest mITT overall cure rate (84%) and achieved 87% when optimised with high-dose PPIs (p>0.05). Quadruple PPI-bismuth-tetracycline-metronidazole achieved optimal eradication rate (91% by mITT), only when high-dose PPIs and 14-day prescriptions were used. The use of doxycycline instead of tetracycline was associated with lower eradication rates in classical bismuth quadruple therapies (p<0.05).

Conclusion

Empirical rescue treatments in third and subsequent lines obtain, in general, suboptimal eradication rates in Europe; however, bismuth quadruple therapy as single-capsule obtained encouraging results. Only the optimised bismuth quadruple therapy achieved ≥90% effectiveness.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.

Clinical Case Summary

Materials and methods: 24-year-old man with an episode of nausea, anorexia and loss of 4-5 kg in a week, which resolved spontaneously without drugs. During the episode had hyperchromic urine, yellowing of skin and eyes.After 1 month small increase of serum transaminases x 1.5. Regular bowel function. No clinical signs. US regular. Anti-HbsAg and HCV-Ab negative. After another month he had highly increase of serum transaminases with AST x 27 and ALT x50 GGT x3, Total bilirubin 2.85. Negative ANA, AMA, LKM, IgA anti TTG, anti EBV, anti CMV, alpha1 anti trypsian slight increase. He performed a new serum analysis with increase of anti-TTG IgA. He subsequently performed genetics for celiac disease and confirmed homozygous DQ2.Performs EGDS for suspected celiac disease which documents nodularity in bulb and DII scalloping. Histological examination shows Marsh 3B.After 150 g gluten daily intake had IgA anti TTG x 4. A diagnosis of celiac disease is made and he started GFD with serum transaminases x 2After 2 months with good adherence to GFD has AST x20 and ALT x 50. He denies alcohol abuse.Negative hemochromatosis mutations. Stable weight, Regular bowel function. We perform liver biopsy. The histological examination documents Histological Activity index acc. Knodell modified by Ishak: 7 Grading.
Results: Diagnosis is moderately active chronic autoimmune hepatitis.Therapy is started with prednisone 40 mg daily. With AST x10 and ALT x 20After 15 days of therapy AST x 5 and ALT x9, therefore values halving and normal bilirubin. Currently under follow-up in our Hospital
Conclusions: Although the history is still unknown and the histological exam is compatible but not certain, the good response to steroid therapy is a positive factor that proves the correctness of the diagnosis. This diagnostic difficulty leads us to always evaluate the autoimmune cause in a young patient without risk factors with a small increase in transaminases.

References

University of Salerno

Clinical Case Summary

Introduction: Gastric siderosis (GS) refers to the abnormal deposition of iron within the gastric mucosa, a condition that can be associated with various underlying pathologies. Our case depicts a case of gastric siderosis with iron deposition in the stomach in association with excessive oral iron intake, presenting unusually with chronic diarrhea. Such association has been mentioned previously in the literature but not established.
Case: A 70-year-old lady with a history of iron deficiency anemia and chronic kidney disease presented with 3 weeks of progressively worsening diarrhea. Home medicines included iron pills. She denied any blood in stool, abdominal pain, recent travel, or antibiotic use. Her vitals and her abdominal exam were unremarkable. Stool studies, including stool parasite, C. difficile toxin, calprotectin, and bacterial PCR, were negative.
Colonoscopy showed a normal macroscopic appearance with random biopsies negative for microscopic colitis. An upper endoscopy was performed demonstrating normal esophagus but pitted brown spots mucosa in the gastric body, and antrum. Biopsies were taken, with antral ones demonstrating antral mucosa with iron deposition in the glands and lamina propria concerning gastric siderosis. Oral iron was discontinued and the patient endorsed improvement in symptoms upon outpatient follow-up with endoscopic resolution at 6 months.
Discussion: Iron deposition in gastric mucosa induces a highly oxidative state, producing injury. However, siderosis due to oral iron use is less commonly associated with mucosal injury, with cases seen with changes ranging from erythema to mucosal erosions. Our patient had pattern B on biopsy involving stroma, whereas A involves macrophages in gastric inflammation, and C involves glands in hemochromatosis. No association with the duration or amount of exposure is associated with differences in symptoms. Non-bloody diarrhea occurs without active ulceration being reported, making our patient unique.

References

1. Marginean EC, Bennick M, et al. Gastric siderosis: patterns and significance. Am J Surg Pathol. 2006 Apr;30(4):514-20. doi: 10.1097/00000478-200604000-00013. PMID: 16625099.
2. Abraham SC, Yardley JH, Wu TT. Erosive injury to the upper gastrointestinal tract in patients receiving iron medication: an underrecognized entity. Am J Surg Pathol. 1999 Oct;23(10):1241-7. doi: 10.1097/00000478-199910000-00009. PMID: 10524525.
3. Siah CW, Ombiga et al. Normal iron metabolism and the pathophysiology of iron overload disorders. Clin Biochem Rev. 2006 Feb;27(1):5-16. PMID: 16886043; PMCID: PMC1390789.
4. Idoate Gastearena MA, et al. A comparative study on the gastroduodenal tolerance of different antianaemic preparations. Hum Exp Toxicol. 2003 Mar;22(3):137-41. doi: 10.1191/0960327103ht330oa. PMID: 12723894.
5. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011 Mar 15;434(3):365-81. doi: 10.1042/BJ20101825. PMID: 21348856; PMCID: PMC3048577.
6. Hattori H. High prevalence of haemosiderin accumulation in the cytoplasm of gastric glands in patients with liver cirrhosis. J Clin Pathol. 2004 Jun;57(6):621-4. doi: 10.1136/jcp.2003.010405. PMID: 15166268; PMCID: PMC1770335.
7. De Petris G, Gatius Caldero S, et al. Histopathological changes in the gastrointestinal tract due to drugs: an update for the surgical pathologist (part I of II). Int J Surg Pathol. 2014 Apr;22(2):120-8. doi: 10.1177/1066896913502229. Epub 2013 Sep 10. PMID: 24021899.

Clinical Case Summary

We present the case of a 50-year-old man with six months of persistent, non-bloody watery diarrhea (8–10 episodes/day), unresponsive to antibiotics and probiotics. His past medical history was unremarkable, he took no home medications, and denied raw meat or fish consumption. Notably, he had recently started working in an animal feed production facility one month before symptom onset. Initial labs showed mild leukocytosis (10.04 x 10³/µL; ULN: 8.77) and mildly elevated CRP (7.5 mg/L; ULN: 3.4). Extensive infectious workup, including CMV serology, Quantiferon, stool cultures for Salmonella, and tests for fungi and parasites (e.g., Giardia), fecal elastase, rectal swabs for Klebsiella pneumoniae carbapenemase and Clostridium difficile returned negative. Colonoscopy and upper GI endoscopy were normal, and biopsies from all intestinal segments showed no pathological findings. He was discharged with partial improvement (3–4 bowel movements/day) and normalized CRP, but was readmitted a week later for worsening symptoms. Repeat blood work, thyroid function, serum calcitonin and inflammatory markers were within normal limits. Intestinal ultrasound showed a tubular descending colon suggestive of nonspecific left-sided colitis; other bowel segments were normal. Stool tests remained negative.Urine toxicology was positive for cannabinoids. Upon further questioning, the patient admitted to regular use over the past eight months, including during both hospitalisations (CUDIT-R score = 12). After cessation of cannabinoid use, diarrhea resolved completely. At 3-month follow-up, he was asymptomatic, with normal bowel habits and labs. He reported only sporadic cannabinoid use at present (CUDIT-R score 7). This case illustrates the potential for chronic cannabinoid use to induce persistent diarrhea mimicking infectious or inflammatory disease. Screening for substance use should be considered in chronic unexplained diarrhea.

Introduction

Helicobacter pylori (H. pylori) is the most widespread infection globally and the main cause of chronic gastritis, peptic ulcer disease, and gastric cancer. Its eradication is primarily managed in primary care. Assessing real-world clinical management practices of H. pylori infection and their adherence to clinical guidelines is essential to inform and optimize treatment strategies.

Aims & Methods

To assess the current H. pylori management strategies followed in Primary Care, we conducted an epidemiological cohort study using data from BIFAP, a Spanish healthcare database containing real-world data on the clinical practice of Primary Care physicians.
Patients aged ≥18 years with a recorded H. pylori infection between January 1, 2003, and June 30, 2023, and a prescription for infection treatment were selected. Two algorithms were developed: one to identify potential cases of H. pylori infection, based on ICD-9/10, and SNOMED CT codes, supplemented by clue words; and another to detect prescribed treatment patterns, constructed from guideline-based recommendations compiled from Spanish and European Consensus Conferences between 1997 and 2022, encompassing 19 possible combinations. A validation process was conducted to confirm the accuracy of infection records through manual review of a random sample of electronic health records. Treatment prescriptions were validated based on active ingredients recorded. We analysed the treatment prevalence stratified by clinical and demographic factors. Continuous and categorical variables were summarized using medians and proportions, respectively. First-line treatments were compared with those of the European Registry on H. pylori Management (Hp-EuReg) to contrast Primary and Specialised (that is, gastroenterologists) Care, respectively.

Results

A total of 211,972 subjects were identified with a H. pylori infection record and, at least, one of the possible treatment patterns. The median age at infection diagnosis was 55 years (IQR, 44-66), with women representing 65%. The most frequent first-line treatments included: proton pump inhibitor (PPI) plus a single-capsule containing bismuth, tetracycline and metronidazole (Pylera®) (PPI+ScBQT) with 36% of cases; PPI, clarithromycin, amoxicillin (PPI+C+A) with 30%; and the combination PPI, clarithromycin, amoxicillin, metronidazole (PPI+C+A+M), with 26%. The most commonly used first-line combination among individuals aged 18-64 years was PPI+ScBQT, as well as in those with a recorded diagnosis of obesity, chronic kidney disease, and in current smokers. However, among individuals aged ≥65 years, as well as in those with a recorded diagnosis of peptic ulcer, the most frequent first-line treatment was PPI+C+A. Comparison between Specialised and Primary Care showed that, since 2013, the use of PPI+C+A by Gastroenterologists has decreased from 40% to less than 1% by 2023, with a similar trend observed in Primary Care, although it remains prescribed in over 10% of cases in 2023. The use of non-bismuth quadruple therapy (PPI+C+A+M) significantly increased since 2015, with a higher proportion in Specialised (40%) compared to Primary Care (30%). ScBQT is currently the most widely prescribed regimen, accounting for approximately 60% of prescriptions in both settings.

Conclusion

H. pylori eradication treatments in Primary Care are heterogeneous, with single-capsule bismuth quadruple therapy being the most prescribed. The use of first-line treatment guidelines has generally aligned with Spanish and European recommendations, although their adoption in Primary Care has been slower than in Specialised Care.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.