About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Prior Exposure to TNF Antagonists May Increase Response to JAK Inhibitors in Patients with Ulcerative Colitis

Posted on October 30, 2025 by gutsandgrowth

HH Lee et al. Clinical Gastroenterology and Hepatology 2025; 23, 2102 – 2114. Open Access! Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists

Methods: Meta-analysis of 17 randomized controlled trials in 8871 adults with moderate-severe UC. The authors calculated the ratio of odds ratio of achieving remission with active drug vs placebo, in TNF antagonist–naïve vs TNF antagonist–exposed patients.

Key findings:

JAK inhibitors: Less efficacious in TNF antagonist–naïve vs exposed patients (6 trials; ratio of OR, 0.47)
IL-23 antagonists: No significant difference was observed in efficacy of selective interleukin-23 antagonists vs placebo in TNF antagonist–naïve vs exposed patients (6 trials; ratio of OR, 1.07)
Lymphocyte trafficking inhibitors: More efficacious in TNF antagonist–naïve vs exposed patients (5 trials; odds ratio [OR], 1.88)

Discussion:

This study “confirmed prior observations that exposure to TNF antagonists significantly reduces the efficacy of lymphocyte trafficking inhibitors in inducing remission, including both vedolizumab and S1P receptor modulators, by approximately 50%.In contrast, prior exposure to TNF antagonists was associated with a significant increase in the efficacy of JAK inhibitors in inducing remission, with 2-fold higher efficacy in TNF antagonist–exposed vs TNF antagonist–naïve patients”
In the SELECT-COMPARE trial in patients with rheumatoid arthritis, there was also an improved response to upadacitinib in patients with prior adalimumab.
“The current findings raise the intriguing possibility that exposure to TNF antagonists could result in lasting effects on the immune system that differentially alter responsiveness to therapies with distinct mechanisms of action”

My take: This study suggests that JAK inhibitors are a good choice for secondary therapy after anti-TNF agents. Other factors, besides efficacy, including safety, extraintestinal manifestations, and cost, have to be considered as well.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Comprehensive ACG Clinical Guidelines for Crohn’s Disease (2025)

Posted on October 29, 2025 by gutsandgrowth

GR Lichenstein et al. The American Journal of Gastroenterology 120(6):p 1225-1264, June 2025. Open Access!! ACG Clinical Guideline: Management of Crohn’s Disease in Adults

Yesterday and Today I am highlighting two adult clinical guidelines both of which are equivalent to up-to-date textbook chapters with specific recommendations; both are open access. In addition, the articles have accompanying author podcasts. Thanks to Ben Gold for these references.

Selected Management Recommendations:

Table 1, #3: We suggest against requiring failure of conventional therapy before initiation of advanced therapy for the management of CD
Table 1, #13: We recommend combination therapy of intravenous infliximab with immunomodulators (thiopurines) as compared with treatment with either immunomodulators alone or intravenous infliximab alone in patients with CD who are naive to those agents
Table 1, #33: In patients with high-risk CD, we recommend anti-TNF therapy to prevent postoperative endoscopic recurrence

Key Concepts:

Table 2, #9: Symptoms of CD do not correlate well with the presence of active inflammation and therefore should not be the sole guide for therapy. Objective evaluation by endoscopic or cross-sectional imaging should be undertaken periodically to avoid errors of under- or over-treatment.
Table 2, #14: The 10-year cumulative risk of major abdominal surgery in CD is 40%–55%, although recent studies performed in the biologic era suggest that the 10-year risk may have decreased to 30%. The 10-year risk of a second resection after the first is 35%, although again more recent studies suggest that this may have dropped to closer to 30%.
Table 2, #15: In CD, the 5-year rate of symptomatic postoperative recurrence is ∼50%.
Table 2, #29: Small bowel imaging should be performed as part of the initial diagnostic workup for patients with suspected CD.
Table 2, #31: Because of the absence of radiation exposure, magnetic resonance enterography should be used preferentially in young patients (younger than 35 years) and in patients in whom it is likely that serial exams will need to be performed.
Table 2, #38: Mucosal healing as determined by endoscopy is a goal of therapy. Scoring systems are available to measure the endoscopic disease activity and may be used to monitor response to therapy.
Table 2, #41: Antibiotics are not an effective treatment for luminal inflammatory CD and should not be used as a primary therapy.

My take: Given the rapid changes in available therapies, it would be optimal to make these collaborative guidelines (AGA, ACG, NASPGHAN) available online with frequent updates (similar to HCVguidelines.org).

Comprehensive ACG Clinical Guidelines for Ulcerative Coliits (2025)

Posted on October 28, 2025 by gutsandgrowth

D Rubin et al. The American Journal of Gastroenterology 120(6):p 1187-1224, June 2025. Open Access! ACG Clinical Guideline Update: Ulcerative Colitis in Adults

Today and tomorrow I am highlighting two adult clinical guidelines both of which are equivalent to up-to-date textbook chapters with specific recommendations; both are open access. In addition, the articles have accompanying author podcasts. Thanks to Ben Gold for these references.

Table 2 in the UC guideline makes 54 recommendations and Table 3 provides 57 key concepts.

Selected Management Recommendations:

Table 2, #4: We recommend treating patients with UC to achieve endoscopic improvement (Mayo score 0 or 1) to increase the likelihood of sustained steroid-free remission and to prevent hospitalization and surgery
Table 2, #5: We recommend the use of FC (fecal calprotectin) in UC to assess response to therapy, to evaluate suspected relapse, and during maintenance
Table 2, #33: When infliximab is used as induction therapy for patients with moderately to severely active UC, we recommend combination therapy with a thiopurine
Table 2, #43: Recommend continuing tofacitinib or upadacitinib as compared with no treatment for maintenance of remission in patients with prior moderately to severely active UC now in remission after induction with tofacitinib or upadacitinib. **The authors recommend continuing each biologic that achieved remission with induction therapy (#38-#43)
Table 2, #51: In patients with ASUC failing to adequately respond to intravenous corticosteroids (IVCS) by 3 days, we recommend medical rescue therapy with infliximab or cyclosporine (Strong recommendation, moderate quality of evidence).

Key concepts:

Table 3, #29: Patients who are primary nonresponders to an anti-TNF (defined as lack of therapeutic benefit after induction and despite sufficient serum drug concentrations) should be evaluated and considered for alternative mechanisms of disease control (e.g., in a different class of therapy) rather than cycling to another drug within the anti-TNF class.
Table 3, #31: Subcutaneous infliximab and vedolizumab are considered equivalent to the standard intravenous maintenance dosing of these agents. The equivalence of the subcutaneous formulations for induction or as substitution for escalated doses of these therapies has not been robustly established.
Table 3, #41: Patients with UC should have available all medical options as recommended by their doctor and healthcare team. Third-party payers and requirements for step therapy should not come between the patient and their healthcare team in making decisions about treatment for UC.
Table 3, #48: All patients with ASUC should undergo a flexible sigmoidoscopy within 72 hours and preferably within 24 hours of admission. This should be used to assess endoscopic severity of inflammation and to obtain biopsies to evaluate for cytomegalovirus (CMV) colitis.
Table 3, #51: Nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics, and medications with anticholinergic side effects should be avoided in ASUC.
Table 3, #57: In patients with ASUC initiating infliximab, dose intensification should be considered for those patients with low serum albumin (<2.5 g/dL).

My take: This article does an excellent job of summarizing current available evidence and good practice. Many of the recommendations may be helpful in garnering approval from third party payers.

Related blog posts:

Medical Imaging of Children/Adolescents and Risk of Cancer (2025)

Posted on October 27, 2025 by gutsandgrowth

R Smith-Bindman et al. NEJM 2025; 393: 1269-1278. Medical Imaging and Pediatric and
Adolescent Hematologic Cancer Risk

Methods: This was a retrospective cohort of 3,724,623 children born between 1996 and
2016 in six U.S. health care systems and Ontario, Canada, until the earliest of cancer
or benign-tumor diagnosis, death, end of health care coverage, an age of 21 years, or December 31, 2017.

Key findings:

During 35,715,325 person-years of follow-up (mean, 10.1 years per person), 2961 hematologic cancers were diagnosed, primarily lymphoid cancers (2349 [79.3%]), myeloid cancers or acute leukemia (460 [15.5%]), and histiocytic- or dendritic-cell cancers
(129 [4.4%]).
The excess cumulative incidence of hematologic cancers by 21 years of age among children exposed to at least 30 mGy (mean, 57 mGy) was 25.6 per 10,000
The authors estimated that 10.1% of hematologic cancers may have been attributable to radiation exposure from medical imaging, with higher risks from the higher-dose medical-imaging tests such as CT

Cumulative Incidence of Hematologic Cancer According to Attained Age and
Radiation Dose to Bone Marrow among Children without Down’s Syndrome

Discussion Points:

“A 15-to-30-mGy exposure equivalent to one to two CT scans of the head was associated with an increased risk by a factor of 1.8”
“Although CT and other radiation-based imaging techniques may be lifesaving, our
findings underscore the importance of carefully considering and minimizing radiation exposure during pediatric imaging to protect children’s long-term health”
“Research on Japanese atomic-bombing survivors showed that leukemia rates peaked 6 to 8 years after exposure, with excess risk lasting for more than five decades, particularly for acute myeloid leukemia”
This study tried to avoid concerns about reverse causation — in which imaging is performed because of existing cancer symptoms –by lagged exposures by 6 and 24 months
“The increasing use of low-value imaging in children and excessive radiation doses in CT are well documented…In many cases, reducing the imaging dose or substituting magnetic resonance imaging or ultrasonography may be more feasible than avoiding imaging altogether”

While the risks in aggregate appear quite substantial, the editorial (L Morton. NEJM 2025; 393; 1337-1339.Studying Cancer Risks Associated with Diagnostic Procedures –Interpret Wisely) makes the point that the risks for the individual are very small. “Fewer than 1% of youths in this study accumulated doses of 30 mGy or more from medical imaging and even at this exposure level, the excess cumulative incidence of hematologic cancers was low (25.6 per 10,000)…we need to ensure that all involved in medical imaging…wisely interpret the results…to understand the balance of the very small risks and the notable benefits of necessary imaging examinations to provide optimal patient care.”

My take: This study is a reminder to carefully evaluate the benefits, risks and alternatives when using ionizing radiation studies.

Related blog posts:

Inability to Burp: How Effective is Botox?

Posted on October 26, 2025 by gutsandgrowth

Briefly noted: S Sanagapalli et al. The American Journal of Gastroenterology 120(9):p 2051-2058, September 2025. Prospective Controlled Study of Endoscopic Botulinum Toxin Injection for Retrograde Cricopharyngeus Dysfunction: The Inability to Belch Syndrome

This study explored a treatment with botulinum toxin (aka. Botox) for people who can’t belch due to a condition called retrograde cricopharyngeus dysfunction (R-CPD), which causes gas-related discomfort. Researchers used high-resolution manometry (HRM) with carbonated drink provocation to diagnose R-CPD. Then, they tested a treatment involving botulinum toxin injections into the cricopharyngeal muscle.

Out of 65 participants, 52 received the treatment, and 92% of those who received the treatment were able to belch after three months, significantly improving their symptoms and quality of life. In contrast, the control group, which included participants who deferred or declined treatment, saw no improvement. After 3 months, 43/51 (84%) of the treatment group reported being satisfied or very satisfied with therapeutic outcome.

Related blog posts:

In the News: Fewer Peanut Allergies, Possibly Improving Obesity Rates in U.S., Best Fruit for Constipation

Posted on October 24, 2025 by gutsandgrowth

10/20/25 NY Times: Peanut Allergies Have Plummeted in Children, Study Shows “The new study, published Monday in the journal Pediatrics, found that food allergy rates in children under 3 fell after those guidelines were put into place — dropping to 0.93 percent between 2017 and 2020, from 1.46 percent between 2012 and 2015. That’s a 36 percent reduction in all food allergies, driven largely by a 43 percent drop in peanut allergies.”

Referenced article (Open Access!): S Gabryszeweki et al. Pediatrics e2024070516. Guidelines for Early Food Introduction and Patterns of Food Allergy

Why Pediatric Patients Need Higher Dosing of Infliximab

Posted on October 23, 2025 by gutsandgrowth

E Stenke et al. Inflamm Bowel Dis 2025; 31: 2331-2337. Higher-Dose Infliximab Induction Achieves Better Maintenance Trough Levels in a National Pediatric IBD Cohort—A Retrospective Study

In this single center retrospective study from Ireland, the authors examined 122 patients (93 with Crohn’s disease [CD], 18 with ulcerative colitis [UC], 1 with IBDU) who received infliximab and had prospectively-collected data. The earlier cohort 2018-2019 received 5 mg/kg/dose and the later group 10 mg/kg/dose. Both groups had proactive therapeutic drug monitoring (pTDM).

Key findings:

The 5 mg/kg group, compared to the 10 mg/kg group, was less likely to have target pre-third TLs (6% vs 80%, P < .001) with the stated goal of >/= 15 microgm/mL
Fewer patients in the 5 mg/kg than 10 mg/kg group had pre-fourth TLs ≥5 µg/mL (6/48 [12.5%] vs 28/50 [56%], P < .001; mean [SD] TL 3.5 [6.3] vs 10.0 [9.9], P < .001)
Concurrent immunomodulator therapy was more common in the 5 mg/kg group (43% compared to 24%)
80% of patients were still receiving infliximab at 1 year including 87% of patients with CD and 54% with UC
The higher dose group had a lower CRP at 1 year followup. 26% of patients receiving the lower dose had a CRP > 5 mg/L compared with 9% in the higher dose group.
Some other measures of long term outcome (eg. IFX durability, clinical remission) were slightly better but did not reach statistical significance (see below)

Discussion Points:

“Our data show higher rates of below-target infliximab levels during and after induction in the 5 mg/kg group. Higher rates of dose escalation in this group during the first year resulted
in similar dosing regimens…Thus, the similar infliximab durability and clinical outcomes
at 1-year follow-up reflect early-dose optimization leading to dose equalization between the 2 groups, rather than a lack of benefit to higher dosing regimens”
“Our data affirm that proactive TDM with pre-emptive dose escalation restores
below-target infliximab TLs and sustains clinical response…Indeed, in our cohort, some patients with low IFX levels pre-third dose were given their fourth dose 6 weeks later, rather
than the standard 8 weeks. Without proactive TDM results, our rate of suboptimal TLs pre-fourth and during maintenance therapy would have been higher in both groups”
“Rates of immunomodulator use in the 10 mg/kg group were lower than in the earlier cohort of 5 mg/kg, reflecting changes in clinical practice over time”

My take:

This study shows that 94% of pediatric patients did NOT achieve adequate levels of infliximab at the pre-third dose with “standard” therapy. This was true even with 43% of the lower dose cohort receiving combination therapy (which often helps improve pharmacokinetics)
Proactive therapeutic drug monitoring helped mitigate the clinical outcomes, especially in the lower dosed cohort
“Children with IBD treated with the historic standard dose of 5 mg/kg induction are at increased risk of pharmacokinetic treatment failure related to high rates of suboptimal TLs”

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Consensus Recommendations on Functional Bloating and Distention

Posted on October 22, 2025 by gutsandgrowth

C Melchior et al. United European Gastroenterology Journal, 2025; 00:1–39. Open Access! European Consensus on Functional Bloating and Abdominal Distension—An ESNM/UEG Recommendations for Clinical Management

A total of 21 experts (authors of article), recommended by ESNM, The European Association for Gastroenterology, Endoscopy and Nutrition (EAGEN) and The European Society for Primary Care Gastroenterology (ESPCG), from different countries agreed to participate as the International Working Group for the European Consensus on Bloating to vote on the Delphi statements.

This article regarding bloating/distension in adults is summarized in two tables. Table 1 has 75 statements. Table 2 is a summary –here are many of its recommendations:

Patients with functional bloating and abdominal distention should receive a lactose‐limiting diet trial based on their self‐reported symptoms or the presence of intolerance during a breath test after ingestion of a defined lactose load

A low FODMAP diet is effective in reducing functional bloating and abdominal distention
Rifaximin may be useful for the treatment of functional bloating and abdominal distention with efficacy
Among antispasmodic agents, pinaverium and otilonium bromide have been shown to be the most effective drugs for the treatment of functional bloating and abdominal distension
Lubiprostone, plecanatide and linaclotide are effective in improving constipation associated with functional bloating and abdominal distension
Linaclotide is the most effective secretagogue for functional bloating, although limited data is available for lubiprostone and plecanatide as well
Selective serotonin reuptake inhibitors (SSRI’s) are effective in reducing symptoms of functional bloating
Tricyclic antidepressants (TCA) such as amitriptyline are effective in reducing symptoms of functional bloating
In patients with discrete episodes of visible abdominal distension, biofeedback‐guided techniques to re‐educate abdominothoracic muscular activity are safe and effective for correction of abdominal distention and are associated with improvement in the subjective sensation of abdominal bloating
“Hypnotherapy improves symptoms of bloating in patients with IBS. However, its effect on functional bloating and abdominal distension was not explored and cannot be recommended”

Figure 1 provides an algorithm. For workup, it suggests checking the following in all patients: TSH, HgbA1c, CBC, CRP, TTG IgA, IgA, Glucose
In those with alarm features (eg. anemia, wt loss, suspicion of organic disease), more extensive evaluation is recommended

My take: One of my colleagues would often say that if there are a lot of treatments for a disease it usually indicates that none of them are very good.

Related blog posts:

New Era in Cholestatic Liver Diseases

Posted on October 21, 2025 by gutsandgrowth

H Sutton, RJ Sokol, BM Kamath. Hepatology 2025; 82: 985-995. Open Access! IBAT inhibitors in pediatric cholestatic liver diseases: Transformation on the horizon?

This review article is one of many in the same issue (#4) of Hepatology.

Key points:

“In the last few years, a novel class of agents, intestinal bile acid transporter (Ileal bile acid transporter (IBAT); also known as apical sodium-dependent bile acid transporter [ASBT]) inhibitors, has emerged and gained approval from the FDA… the pivotal studies on which these approvals were granted were all performed in rare pediatric cholestatic diseases, namely Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC).³ Additional expansion of these approvals will possibly follow as there are ongoing trials of IBAT inhibitors in primary biliary cirrhosis, primary sclerosing cholangitis, and biliary atresia.”
“The role of bile acids in promoting hepatic injury in cholestasis is perhaps best illustrated in human infants with ABCB11 (bile salt export pump; BSEP) disease or PFIC type 2…The response to IBAT inhibition in this disease further supports the notion that retained bile acids are a key factor leading to progressive liver injury and cholestatic symptoms including pruritus, fat-soluble vitamin deficiencies, and growth failure.⁴“
These medications may improve liver histology and not just reduce pruritic symptoms: “Using the MDR2^−/− mouse cholangiopathy model, Miethke et al²² demonstrated that ASBT inhibition led to a reduction in both serum and intrahepatic bile acid concentrations by 98% and 65%, respectively. These reductions in bile acid concentrations were associated with improved liver biochemistry and a reduction in peri-portal inflammation and fibrosis on histology. The histopathologic improvements seen in these treated MDR2^−/− are important to highlight, as they support the rationale of this therapeutic approach: that lowering serum bile acid (sBA) with IBAT inhibition leads to a reduction in intrahepatic bile acid accumulation and toxicity, improvements in liver inflammation and fibrosis, and ultimately improved liver disease biology.”
Numerous clinical trials are listed in Table 1 (completed trials) and Table 2 (ongoing).
Physiology: “Bile acids are key regulators of their own enterohepatic circulation, predominately through activation of the farnesoid X receptor (FXR)…the fecal elimination of bile acids in IBAT inhibitor–treated patients appears to far exceed the rate of synthesis of new bile acids in the liver; thus, IBAT inhibitors reduce the total bile acid pool size and the bile acid load presented to the liver.^22,34,39“
Alagille syndrome (ALGS): Key trials are summarized including the ICONIC trial with maralixibat and the ASSERT trial with odevixibat.
PFIC (Type 1 and 2) Trials: Key trials are summarized including the MARCH-PFIC trial with maralixibat and the PEDFIC1 & PEDFIC 2 trialswith odevixibat.
Safety: These medications are well-tolerated with self-limiting diarrhea and abdominal pain especially at the initiation of these medications. Liver blood test abnormalities have been noted in up to 20%. “This is an interesting finding, and the underlying etiology is unknown. Maralixibat is largely luminally restricted and so, without systemic absorption, a direct hepatotoxic effect is unlikely. It may reflect an alteration in the speciation of the bile acid pool with increasing bile acid synthesis or alterations in the gut-liver axis signaling. More importantly, it is not known if there are any clinical consequences to the increase in ALT.”
Cost: The authors note that ursodeoxycholic acid and antihistamines are frequently used for management of pruritus. They also not that “from a cost standpoint, it seems appropriate to offer rifampin before IBAT inhibitors in the treatment of cholestatic pruritus.”
Conclusions: “The clinical trial data are encouraging. As more physicians gain experience prescribing IBAT inhibitors, we will continue to learn how to best apply them to our patient populations. Like any new drug, there are still several unknowns. One of these unknowns is the potential for loss of efficacy…The short-term to medium-term clinical effects of IBAT inhibitors are clear, but we have not yet begun to see the long-term benefits. Whether durable reductions in oncogenic and fibrogenic bile acids reduce rates of HCC or slow the progression of (or reverse) portal hypertension remains to be seen.”

Related article: M Trauner, SJ Karpen, PA Dawson. Hepatology 2025; 82: 855-876. Open Access! Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease

“Recent advances in understanding bile acid (BA) transport in the liver… This has led to new treatments targeting BA transport and signaling. These include inhibitors of BA transport systems in the intestine and kidney (IBAT/ASBT inhibitors) and liver (NTCP inhibitors), as well as receptor agonists that modify BA synthesis and transport genes. BA analogs like norucholic acid also show promise. This review discusses the molecular and clinical basis for these therapies, particularly for cholestatic liver disorders.

Principal therapeutic targets within the entero-nephro-hepatic circulation of BAs in cholestasis.

My take (borrowed from Trauner et al): “We have arrived at a new era in the treatment of cholestatic disorders. This has been made possible by incorporating findings from discoveries into the molecular pathogenesis of cholestasis and adaptive processes that direct rational therapeutics to improve patients’ lives.”

Related blog posts:

NSAIDs for Severe Acute Pancreatitis

Posted on October 20, 2025 by gutsandgrowth

L Huang, et al. Gut 2025;74:1467–1475. doi:10.1136/gutjnl-2024-334038. Open Access! Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial

Background: “COX-2 inhibitors (COX-2-Is) have shown potential in reducing pancreatitis severity and improving renal and respiratory function in animal models.” However, at this time, “there is no effective drug treatment for organ failure (OF) caused by severe acute pancreatitis (SAP)” in humans.

Methods: “In this multicentre, double-blind, randomised, placebo-controlled, investigator-initiated trial, 348 patients with acute pancreatitis aged 18–75 years, <1 week from onset of illness to admission, and Acute Physiology and Chronic Health Evaluation II Score ≥7 or modified Marshall Score ≥2, were randomly assigned (1:1) to the COX-2-Is group (parecoxib sequential with imrecoxib) or the placebo group.”

The authors chose to adopt a sequential regimen of intravenous (3 days) to oral COX-2-Is. “Parecoxib labelling recommends intravenous administration for no more than 3 days due to limited clinical experience beyond this period.”

Key findings:

“Compared with the placebo group, SAP occurrence was reduced by 20.7% (77.6% vs 61.5%, p=0.001) and the persistent OF duration in SAP was shortened by 2 days (p<0.001) after COX-2-Is treatment.”
“For patients enrolled within or after 48 hours from symptom onset, SAP occurrence was reduced by 23.8% (p=0.001) and 8.5% (p=0.202), and the persistent OF [organ failure] duration in SAP was shortened by 3 days (p=0.001) and 2 days (p=0.010) after COX-2-Is treatment, respectively.”
“The serum levels of inflammatory mediators and 30-day mortality (from 8.6% to 3.4%) were significantly reduced after COX-2-Is treatment, p<0.05.”
“The incidence of adverse events was similar between the two treatment groups.”

My take: This study showed that NSAIDs (starting with IV x 3 days) improved outcomes with severe acute pancreatitis (in adults). Prior studies have also showed reduced pancreatitis with NSAIDs following ERCP.

Related blog posts:

Ketorolac After ERCP -Pediatric Study IFor high-risk pediatric patients with injection of contrast into and/or cannulation of the pancreatic duct, the rates of PEP were significantly lower for patients who received ketorolac (11% vs 25%, P = 0.035)
Indomethacin to prevent post-ERCP pancreatitis
A$$inine Pricing of Indomethacin Suppositories
How to Upgrade Pancreas Care –Jay Freeman MD (Part 1)
How to Upgrade Pancreas Care –Jay Freeman MD (Part 2)
Acute Pancreatitis: Clinical Report from NASPGHAN