Tag Archives: inflammatory bowel disease

Antibiotics and IBD Risk: A Systematic Review

Posted on by

R Duan et al. Clin Gastroenterol Hepatol 2025; 23: 45-58. Open Access! Antibiotic Exposure and Risk of New-Onset Inflammatory Bowel Disease: A Systematic Review and Dose-Response Meta-Analysis

Twenty-eight studies involving 153,027 patients with IBD were included.

Key findings:

  • Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29–1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08–1.68). ‘
  • This association existed for both Crohn’s disease and ulcerative colitis, as well as in children and adults for prescription-based studies. 

Some of the limitations:

  1. There was statistical heterogeneity was high in the primary analysis, possibly because of inconsistencies in study design
  2. Most studies included a clear lag time, yet an inadequate lag time still creates the possibility of reverse causality.
  3. The authors could not disentangle the risk of antibiotics from the risk of infection in leading to the development of IBD.
Nonlinear dose-response relationship between antibiotic exposure and risk of new-onset IBD (solid black line and short dash black line represent estimated ORs and corresponding 95% CIs of nonlinear relationship)

My take: This is another study showing an association between antibiotic use and new-onset IBD. While this study does not prove causation, it is another reason for good antibiotic stewardship.

Related blog posts:

ESPGHAN Guidelines for PSC in Children

Posted on by

PF van Rheenen et al. JPGN 2024; DOI: 10.1002/jpn3.12378. Open Access! Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group

Recommendations:

  • In children with suspected or confirmed IBD, screening for liver disease is usually performed at 3 to 6 months intervals and a work‐up for underlying liver disease is most commonly initiated when liver enzymes exceed 2x the upper limit of normal
  • Use MRCP as the radiological modality of choice for diagnosing PSC
  • Consider performing a liver biopsy in children with IBD and suspected PSC in the following circumstances: i) Normal biliary tree at MRCP, ii) raised immunoglobulin G and the presence of liver-specific autoantibodies, or iii) clinical uncertainty before steroid induction therapy for IBD
  • Perform fecal calprotectin screening at least once yearly in children with isolated PSC and/or AIH to select patients for diagnostic endoscopy for suspected inflammatory bowel disease (panel recommends cutoff of >150 indicating need for ileocolonoscopy)
  • Surveillance colonoscopy should be considered in children with PSC–IBD and the following risk factors of colorectal cancer: i) persistent active colonic inflammation, ii) longstanding colitis (≥8 years), or iii)  a family history of colorectal cancer in a first-degree relative <50 years. (The overall risk of colon cancer in those <18 yrs of age is very low)
  • UDCA may be prescribed at doses of 15–20 mg/kg/day. Despite evidence of improvement of liver enzymes, its long-term effect on disease progression has not been demonstrated. Consider a 6-months therapeutic trial of UDCA, either immediately after PSC diagnosis or when spontaneous normalization of GGT does not occur in the first 6 months postdiagnosis. Continue UDCA treatment if there is a meaningful reduction or normalization of GGT or improvement of symptoms
  • Oral vancomycin may be prescribed for a potential improvement in liver biochemistry as well as bowel inflammation. Its long-term effect on disease progression has not been demonstrated
  • In children with PSC–IBD and biochemical, serological, and histological features of AIH, the use of corticosteroids and antimetabolites may suppress immune-mediated hepatitis. In the absence of convincing AIH features, the use of corticosteroids and antimetabolites is not indicated to manage PSC
  • Children with PSC, relevant bile-duct strictures and cholestatic symptoms should be assessed for liver transplantation. When their symptoms are likely to improve following biliary intervention, ERCP can be considered
  • Recommended blood testing for children with PSC: At diagnosis: Autoantibodies (ANA, anti-SMA, anti-LKM-1, anti-LC1, and anti-SLA), Every 3-6 months: ALT, AST, GGT, Albumin, INR, Platelets, CRP. Every 12 months: IgG, AFP, and Fat Soluble vitamins. Consider f/u autoantibodies in those with elevated IgG at f/u lab testing

My take: This is a useful position paper; it does not have a zillion recommendations like some other ESPGHAN positions papers. Given the frequency of liver enzyme elevation in patients with IBD, mild to modest elevations may need to be observed before launching an extensive evaluation (see related blog posts below).

Related blog posts:

Key Advances in 2024: An Overview from GutsandGrowth (Part 1)

Posted on by

This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Is Breastfeeding Linked to IBD Risk in Offspring?

Posted on by

M Agrawal et al. Clin Gastroenterol Hepatol 2024; 22: 2459-2467. Open Access! Breastfeeding Duration Is Not Associated With Offspring Inflammatory Bowel Disease Risk in Three Population-Based Birth Cohorts

The authors utilized  prospectively collected data from 3 population-based birth cohorts (Danish National Birth Cohort, Norwegian Mother, Father, and Child Cohort, and All Babies in Southeast Sweden). This collectively included nearly 170,000 offspring.

Key findings:

  • During median follow-up of 16.3–22.3 years, between 1996 and 2021, 543 offspring were diagnosed with IBD
  • In each country, there was no association between exclusive breastfeeding duration and offspring IBD risk

Discussion:

“In contrast to majority of case-control studies, both cohort studies reported null association between breastfeeding, treated as a binary exposure (any versus no breastfeeding) or by duration, and offspring IBD risk. Similarly, 2 nested case-control studies, leveraging prospectively collected data on early life exposures as part of the population-based Jerusalem Perinatal Study and 2 United Kingdom birth cohorts (the 1946 National Survey of Health & Development and the 1958 National Child Development Study) reported null associations between breastfeeding and IBD risk.22,23 Data from these studies, which are more rigorous in methodology compared with case-control studies, are consistent with findings from our analyses.”

My take: While this study has some limitations inherent in observational data, this study with prospectively-collected data indicates that breastfeeding did not modulate the risk of developing IBD.

Related blog posts:

La Fortuna, Costa Rica

Vancomycin for Inflammatory Bowel Disease in Patients with Primary Sclerosing Cholantgitis

Posted on by

E Ricciuto et al. Aliment pharmacol ther 2024; 59: 1236-1247. Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium

This was a retrospective study from 54 centers with 113 PSC-IBD pediatric patients receiving vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Clinical remission was defined as physician global assessment (PGA) of zero. It is noted that the Pediatric PSC consortium included 1362 patients at the time of this study; only 11% (n=113) were treated with vancomycin for at least 3 months. The median dose of vancomycin was 17 mg/kg/day and median duration was 2.5 years.

Key findings:

  • Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22).
  • Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher hemoglobin and albumin (both p < 0.01).
  • At baseline, prior to vancomycin, 34% (30/88) were in clinical remission; this increased to 60% (52/86) after 6 months of treatment. After ~ 1 year, 71% (55/78) of children treated with vancomycin were in remission, compared with 35% who had not receive the antibiotics.
  • Ursodeoxycholic acid use: 53% for vancomycin-treated and 82% of control group (P<0.001). Other cotherapies were similar including infliximab (36% vs. 27%) and vedolizumab (13% vs 7%)
  • Only 28 vancomycin-treated patients had baseline and f/u colonoscopy data available. 46% of this subgroup had endoscopic remission compared to 26% of matched untreated controls.

In the discussion, the authors acknowledge the limitations of a retrospective observational study. RCTs are quite difficult with rare disorders, especially in children. In addition, the exact mechanisms for vancomycin efficacy remain unclear -possibly microbial changes or its effects on bile acids. They note that many patients treated with vancomycin had mild clinical activity at baseline. Though, even this population may benefit with resolution of clinical inflammation which could reduce the risk of colorectal cancer.

My take: In patients with PSC-IBD, the use of vancomycin for IBD should be a consideration especially in those who have not responded adequately to other treatments.

Related blog posts:

A Treatment for Severe Fatigue Associated with Inflammatory Bowel Disease?

Posted on by

The proverb “Necessity is the mother of invention” is often attributed to Plato. In the dialogue of The Republic, Plato wrote, “our need will be the real creator”. This quote came to mind as I was reading about the use of f for fatigue in inflammatory bowel disease (IBD).

CD Moulton et al. Clin Gastroenterol Hepatol 2024; 22: 1737-1740. Open Access! Modafinil for Severe Fatigue in Inflammatory Bowel Disease: A Prospective Case Series

Background: “Fatigue is highly prevalent in patients with IBD, affecting 72% of patients with active inflammatory bowel disease (IBD) and 47% in remission, and is associated with poor quality of life, absenteeism and presenteeism.1 However, understanding the mechanisms of IBD fatigue remains limited, as reflected in a lack of effective treatments.1“

Methods: “Ten patients with IBD and severe fatigue were referred to a consultant psychiatrist. In all cases, mucosal inflammation and organic causes of fatigue (anemia, B12 deficiency, hypothyroidism) had been investigated and treated as much as possible. We measured fatigue severity using the IBD Fatigue Assessment Scale (IBD-FAS), designed specifically for IBD.5 Scores of 11 or higher out of 20 indicate severe fatigue and we only included patients scoring in this range.5

Dosing (for adults) of modafnil is described in the article.

Key findings:

  • “At baseline, the mean IBD-FAS score was 16.0 (SD, 1.7) of 20. After modafinil treatment [at 6 months], the mean IBD-FAS score was 6.7 (SD, 3.0), representing a mean improvement of 58.1% from baseline.”
  • “Although all 10 patients were severely fatigued at baseline, only 2 patients were still in the severe fatigue range after treatment.”
  • “Tolerability was good: 1 patient reported transient headache and 1 patient reported transient dizziness; another patient reported mild palpitations; but none of the patients reported gastrointestinal side effects.”

My take: Perhaps, modafinil will be helpful –pharmacologic therapy for severe fatigue is an unmet need. More studies are needed as this is a small study without a control group.

Related blog posts:

Acute Pancreatitis in Children with Inflammatory Bowel Disease

Posted on by

A Anafy et al. JPGN 2024; 79:325–334. Acute pancreatitis in children with inflammatory bowel disease: Risk factors, clinical course, and prognosis

In this retrospective study with 376 children, Key Findings:

  • 4% of patients with pediatric IBD developed acute pancreatitis (AP)
  • The presumed etiology for AP in all IBD patients was IBD-related: IBD flare-up in five, side effects of medications in two, and undetermined in seven. 
  • The only risk factor for AP development among IBD patients was IBD‐associated arthritis (23% vs. 3% for IBD‐non‐AP).
  • Extracolonic Crohn’s disease emerged as a negative risk factor for AP: it was present in only 2/13 (15%) IBD‐AP patients compared to 20/39 (51%) IBD‐non‐AP patients (p = 0.05). Patients who receive induction therapy with nutrition (exclusive enteral nutrition or Crohn’s disease exclusion diet) were less likely to be present in the IBD‐AP group (1/12 [8%] vs. 17/39 [44%] IBD non-AP patients, p = 0.04.
  • This study population, at the time of AP, had a relatively high number treated with ASA agents (66%; 11/14 AP-IBD and 26/42 Non-AP-IBD)), 27% with azathioprine (6/14 with AP-IBD and 9/42 Non-AP-IBD), and low number receiving biologics (18%, 2 AP-IBD and 8/42 Non-AP-IBD

My take: This study shows that acute pancreatitis is common in children with inflammatory bowel disease.

Lean Patients with Inflammatory Bowel Disease Have Higher Risk of Steatotic Liver Disease Than Lean Patients Without IBD

Posted on by

SJ Martinez-Dominguez et al. Inflammatory Bowel Diseases, Volume 30, Issue 8, August 2024, Pages 1274–1283, https://doi.org/10.1093/ibd/izad175 Open Acess! Inflammatory Bowel Disease Is an Independent Risk Factor for Metabolic Dysfunction–Associated Steatotic Liver Disease in Lean Individuals 

Methods: This was a cross-sectional, case-control study including 300 lean cases with IBD and 80 lean controls without IBD, matched by sex and age (median age ~45 yrs). All participants underwent a liver ultrasound, transient elastography, and laboratory tests. All patients with current or previous use of systemic steroid in the last 2 years were excluded from the analysis

Key Findings:

  • The lean IBD group showed a significantly higher prevalence of MASLD compared with lean non-IBD group (21.3% vs 10%; P = .022), but no differences were observed in the prevalence of significant liver fibrosis (4.7% vs 0.0%; P = 1.000)
  • No differences were found between the prevalence of MASLD in IBD and non-IBD participants who were overweight/obese (66.8% vs 70.8%; P = .442)
  • IBD was an independent risk factor for MASLD in lean participants (odds ratio [OR], 2.71) after adjusting for classic metabolic risk factors and prior history of systemic steroid use
Prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) in cases and controls according to body mass index (BMI) status. Blue bars: cases (inflammatory bowel disease). Red bars: controls (non–inflammatory bowel disease). P values in bold indicate statistical significance (P < .05).

My take: This study suggests that “chronic inflammation could play a role in MASLD development.” Also, this indicates that MASLD could be a reason for elevated LFTs in patients with IBD, even in lean patients.

Related blog posts:

Predicting the Burden of IBD Until 2040

Posted on by

R Patel et al. Inflamm Bowel Dis 2024; https://doi.org/10.1093/ibd/izae020.067. DECIPHERING THE BURDEN OF INFLAMMATORY BOWEL DISEASE LANDSCAPE (1990-2019) IN HIGH INCOME NORTH AMERICA: PROJECTIONS, TEMPORAL SHIFTS, AND A GLIMPSE BEYOND TO 2040 

Methods: “Utilizing Global Burden of DIsease tool, we estimated IBD prevalence, incidence, mortality, and Disability Adjusted Life Years (DALYs) of IBD in High-Income North America. Standardized statistical techniques facilitated comparisons by age, sex, year within this specific region. The DisMod-MR 2.1 tool was employed to estimate incidence and prevalence, while mortality rates were discerned using the Cause of Death Ensemble Model (CODEm). Additionally, we projected the deaths and Years of Life Lost (YLLs) up to 2040 using regression analysis.”