Category Archives: Uncategorized

Alcohol Burden in Hepatology

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As an outside observer, I wonder how practitioners in the field of adult hepatology feel about the changing epidemiology of severe liver disease.

Case (article) in point: G Cholankeril et al. Hepatology 2021; 74: 3316-3329. Open Access: Impact of COVID-19 Pandemic on Liver Transplantation and Alcohol-Associated Liver Disease in the USA

This retrospective study utilized UNOS adult data from 6/1/19 to 3/1/21. This included 9528 in the pre-COVID era and 9259 in the COVID era.

Key findings:

  • There was “a significant reduction in the monthly listing rates for HCV (−21.69%, P < 0.001) and NASH (−13.18%; P < 0.001).” However, there “was a significant increase in ALD [alcohol-associated liver disease] listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic.”
  • “In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%).”
  • Interestingly, “patients with ALD had a 50% higher probability rate of LT [liver transplantation] than patients with other liver disease.”

The authors note that patients with alcohol use disorder (AUD) and ALD, during the pandemic, “may no longer have structured non-alcohol-related activities and in-person behavioral counseling…coupled with the delay in routine health care…Few patients with ALD receive recommended care for AUD.”

My take: Due to the cumulative effects of ALD, there is likely to continued (worsening) high rates of liver failure due to ALD. Given the difficulties in managing ALD, aside from managing liver complications, this must be a huge emotional burden for many healthcare providers watching this tragedy play out on a continual basis.

Cumulative incidence rates for LT among patients listed for ALD and non-ALD
in the pre-COVID and COVID eras.

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Epidemiology of Gastroparesis in Adults

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Briefly noted: Y Ye et al. Gastroenterol 2022; 162: 109-121. Open Access: Epidemiology, Etiology, and Treatment of Gastroparesis: Real-World Evidence From a Large US National Claims Database

Key findings:

  • The overall standardized prevalence of gastroparesis was 267.7 per 100,000 US adults, whereas prevalence of “definite” gastroparesis (individuals diagnosed within 3 months of gastric emptying scintigraphy testing with persistent symptoms for more than 3 months) was 21.5 per 100,000
  • Etiology was most commonly due to diabetes (57.4%; type 1, 5.7% and type 2, 51.7%), followed by postsurgical (15.0%), drug-induced (11.8%), and idiopathic (11.3%) etiologies

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PSC in IBD

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Briefly noted: B Barberio et al. Gastroenterol 2021; 161: 186-1877. Prevalence of Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Key findings: Overall, pooled prevalence of PSC in IBD was 2.16%; the pooled prevalence was significantly higher in UC versus CD (OR 1.69)

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Microbiome Therapy (SER-109) for Recurrent Clostrioides Difficile

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P Feuerstadt et al. N Engl J Med 2022; 386:220-229. DOI: 10.1056/NEJMoa210651. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection

Background: “SER-109, an investigational oral microbiome therapeutic composed of live purified Firmicutes bacterial spores, was developed to reduce the risk of C. difficile infection recurrence.14 We hypothesized that these spore-forming bacteria would compete metabolically with C. difficile for essential nutrients, modulate bile-acid profiles to reestablish resistance to colonization, or have both of these effects. Here, we report the 8-week efficacy and safety results from a phase 3 [double-blind, randomized, placebo-controlled] trial involving patients with recurrent C. difficile infection, along with supportive microbiome engraftment and metabolomic analyses.”

Methods: N=182 enrolled in the “ECOSPOR III” trial; all patients had at least 3 infections in past year and positive toxin test. After standard-of-care antibiotic treatment, patients received SER-109 or placebo (four capsules daily for 3 days). The primary efficacy objective was to show superiority of SER-109 as compared with placebo in reducing the risk of C. difficile infection recurrence up to 8 weeks after treatment.

Key findings:

  • The percentage of patients with recurrence of C. difficile infection was 12% in the SER-109 group and 40% in the placebo group (relative risk, 0.32)
  • The recurrence risk following SER-109 was even lower after fidaxomicin than vancomycin: relative risk, 0.09 [95% CI, 0.01 to 0.63] with fidaxomicin and 0.41 [95% CI, 0.22 to 0.79] with vancomycin
  • SER-109 dose species were detected as early as week 1 and were associated with bile-acid profiles that are known to inhibit C. difficile spore germination.

My take: This study shows that clinical outcomes with C difficile may be improved by the addition of this microbiome therapeutic after standard therapy. Engraftment of Firmicutes bacteria as a dominant component of the microbiome is generally associated with a healthy state. This opens the door for treatment of other conditions that may benefit from microbiome modulation.

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NASPGHAN 2021 Nutrition Highlights

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Thanks to Kipp Ellsworth for forwarding this link:

Nutrition for IBD website: NASPGHAN 2021 Nutritional Highlights

On this website: “Four presentations/lectures were released at the Nutritional Therapy for IBD Virtual Booth that provide a comprehensive review and update of the latest information regarding the use of EEN and therapeutic diets in the management of IBD”

Why Do We Need Dietary Therapies for IBD

Presenter: Lindsey Albenberg, DO

Dr. Lindsey Albenberg, a clinician and researcher from Children’s Hospital of Philadelphia, describes the rapidly increasing incidence of IBD and its relationship to diet, microbiome and the immune system. She reviews the rationale and science supporting the use of dietary therapy to compliment drug therapy as an avenue to potentially achieve higher, more sustainable and possibly safer levels of remission long term in pediatric patients.

The Crohn’s Disease Exclusion Diet Updates: December 2021

Presenter: Rotem Sigall Boneh, RD. Rotem Sigall Boneh, RD, a primary researcher and developer of CDED, provides an overview of the accumulating data with CDED in combination with PEN, including the newly published results of adult data with important endoscopic findings and further shares real world experience and application of nutritional therapy.

IBD Anti-inflammatory Diet or IBD-AID: Proof of Concept

Presenter Ana Maldonado-Contreras, MSc, PhD. Dr. Ana Maldonado-Contreras, a lead researcher in IBD-AID explains the relationship between diet, microbiome and immune function with the design and rational of IBD-AID to manipulate the microbiome. She shares the recently published data of the impact of IBD-AID on the microbiome and cytokine levels specific to food components.

Nutritional Therapy: Perioperative + Complicated Crohn’s Disease

Presenter Andrew S. Day, MB, ChB, MD, FRACP, AGAF

At the NTforIBD Nutritional Symposium prepared for NASPGHAN2021, Professor Day provides insight into the important role of EEN, an underutilized option to both induce remission and improve outcomes in complicated and peri-operative patients.

Austin Bradford Hill, PPIs and IBD

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KH Allin, P Moayyedi. Gastroenterol 2021; 161: 1789-191 (editorial). Open Access: Proton Pump Inhibitor Use: A Risk Factor for Inflammatory Bowel Disease or an Innocent Bystander?

This editorial helps provide needed context on the associated observational study by Xia et al (B Xia, M Yang et al. Gastroenterol 2021; 161: 1842-1852. Open Access. Regular use of proton pump inhibitor and the risk of inflammatory bowel disease: pooled analysis of 3 prospective cohorts) which showed a mild increase risk of IBD among PPI users. While the PPI users were at 42% increased risk of IBD compared to nonusers, if correct, “the absolute risk associated with PPI use is modest. Number needed to harm is 3770, meaning that when 3770 individuals are treated with PPIs for 1 year, 1 additional case of IBD is observed.”

Despite the efforts of the study authors to minimize confounders, the editorial focuses on the work of Austin Bradford Hill (Proc R Soc Med. 1965; 58: 295-300. The environment and disease: association or causation?) who “realized making causal inferences on observational data was challenging and outlined a list of factors that would make this interpretation more or less likely….strength of association, dose response, and consistency are important and often not commented on in observational studies.”

In a previous “a double-blind, randomized clinical trial comparing pantoprazole with placebo over 3 years with more than 53,000 patient years follow-up found there was no association” with IBD identified…Interestingly, this trial reported a slightly higher risk of enteric infections, and this is the underlying mechanism proposed for how PPI therapy may increase the risk of IBD.”

My take (borrowed from editorial): “Most associations for PPI and harm are likely to be residual or unmeasured confounding, whether this is also true for IBD will only be determined by further study.”

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IBD Updates: Fatigue Trajectory, Risk of IBD with Derm Findings

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NZ Borren et al. Inflamm Bowel Dis 2021; 27: 1740-1746. Open Access: Longitudinal Trajectory of Fatigue in Patients With Inflammatory Bowel Disease: A Prospective Study

In this prospective study using the CCFA IBD Partners cohort, the authors examined fatigue symptoms with questionnaires (FACIT-F and MDI) at 3 timepoints over a 1 year period. There was likely a strong selection bias among participants (mean disease duration was 18 years) who chose to complete theses questionnaires. Key findings:

  • Persistent fatigue (at baseline and at 6 months) was the most common pattern, affecting two-thirds (65.8%) of patients
  • The strongest predictor of incident fatigue was sleep disturbance at baseline (odds ratio, 2.91.
  • Only 12.3% of those with fatigue at baseline had symptom resolution by 6 months. Resolution was more likely in patients with a diagnosis of ulcerative colitis, quiescent disease, and an absence of significant psychological comorbidity

My take: In those with fatigue, it is often persistent.

Related blog post: #MondayNightIBD and Fatigue

D King et al. Inflamm Bowel Dis 2021; 27: 1731-1739. The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel Disease

The authors retrospectively studied 7447 patients with dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet’s syndrome, and aphthous stomatitis which can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs).

Key findings:

  • 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs
  • Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs

My take: The absolute risk if IBD is low in patients with D-EIMs but still increased 6-fold. This would probably be a good population to screen for IBD with a biomarker (eg. calprotectin)

Related blog post: Review of Pyoderma Gangrenosum

J Shah et al. Inflamm Bowel Dis 2021; 27: 1832-1838. Ocular Manifestations of Inflammatory Bowel Disease Nice review: “ocular manifestations of IBD include keratopathy, episcleritis, scleritis, and uveitis and are among the most common extraintestinal manifestations.” Urgent referral to ophthalmology needed if deep eye pain that can awaken from sleep (?scleritis), if photosensitivity/blurry vision/headache (?anterior uveitis), or if floaters/decreased vision (?posterior uveitis)

Functional Abdominal Pain in Children with Celiac Disease

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F Cristofori et al. Clin Gastroenterol Hepatol 2021; 19: 2551-2558. Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet

This prospective cohort (2016-2018, n=417, mean age 13.7 y) examined the frequency of functional disorders (based on questionnaire) in children with celiac disease (CD) who were receiving a strict gluten free diet (GFD) for at least one year.

Key findings:

  • Functional abdominal pain disorders (FAPDs) had a higher prevalence s among patients with CD (11.5%) than controls (6.7%)  (P < .05)
  • Irritable bowel syndrome (IBS) and functional constipation (FC) defined by the Rome IV criteria were more prevalent in patients with CD (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P < .05 and P < .001, respectively)
  • Younger age (P < .05) and a higher level of anti–transglutaminase IgA at diagnosis (P < .04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration
  • A GFD did help with abdominal pain: After starting a GFD, 80% of children with celiac disease had resolution of stomach pain, whereas 9% started to complain of symptoms after starting a GFD

In the discussion, the authors speculate on the reasons for ongoing pain including inadvertent gluten exposure, intestinal inflammation/visceral hyperalgesia, altered microbiome, and refractory CD.

My take: Persistent stomach pain in CD is a common occurrence, even in those trying to adhere to a strict GFD.

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Chattahoochee River, Atlanta

Why I No Longer Need to Be A Billionaire

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For the past few years, when someone would ask me what I would do if I were incredibly wealthy, I would say that I wanted to start a pharmaceutical company to provide reasonably-priced medications. A good example of the problems with drug pricing was discussed earlier in the week on a prior blog post regarding insulin (Insulin: “Poster Child For Everything That’s Wrong” with U.S Drug Costs). Fortunately, I no longer need to be a billionaire:

NPR: (Jan 24, 2022): Billionaire Mark Cuban launches online pharmacy aimed at lowering generic drug prices

An excerpt:

The Mark Cuban Cost Plus Drug Company announced the opening of its online pharmacy Wednesday. The pharmacy says it will bypass health care industry “middlemen” and help consumers avoid high drug prices by charging manufacturers’ prices plus a flat 15% markup and pharmacist fee…

The pharmacy doesn’t accept health insurance but says prices will still be lower than what people would typically pay at a pharmacy….

The website currently offers 100 generic drugs to treat a variety of illnesses, including diabetes, asthma and heart conditions.

One drug for diabetes patients, metformin, sells for $3.90 for a 30-day supply, compared to a retail price of $20, the pharmacy said. A 30-count of imatinib, which is used to treat leukemia and other cancers, goes for as low as $17.10 at Cuban’s pharmacy compared with $2,502.60 at other pharmacies.

Link to Mark Cuban’s Company: Cost Plus Drug Company

GI Medications:

  • Colcichine is priced at $8.70 (retail $176.23)
  • Entecavir $46.20 (retail $995.75)
  • Esomeprazole Capsule (40 mg) $6.00 (retail $216.66)
  • Lansoprazole Capsule (15 mg) $9.00
  • Mesalamine (Generic for Canasa) $36.90 (retail $959.07)
  • Mesalamine (Generic for Apriso) $36.60 (retail $122.57) ***this is only for 30 pills
  • Methotrexate 2.5 mg (30 capsules) $13.80
  • Omeprazole 40 mg capsules $4.50
  • Pantoprazole is priced at $4.50 (40 mg tablets) (retail $71.40)

GoodRx website also has low prices on many of these medications as well; however, some of these prices at the Mark Cuban pharmacy are terrific. For example, the cost of mesalamine suppositories at GoodRx are about three times as much.

My take: I need to talk to our Epic champion to connect our EMR to this pharmacy service.

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IBD Shorts: High TNF levels, Biologics in Pregnancy, & Ileocolic Resection Outcomes in Pediatrics

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M Zvuloni et al. JPGN 2021; 73: 717-721. Open Access PDF: High anti-TNFa Concentrations Are Not Associated With More Adverse Events in Pediatric Inflammatory
Bowel Disease

Key findings (retrospective study):

  • Higher trough concentrations (TCs) (>10 mcg/mL) of anti-TNFa were not associated with higher rate of anti-TNFa-related adverse events in 135 patients & >1500 TC measurements
  • Out of the 30 patients who presented with elevated transaminases, 27 (90%) patients had normalized transaminases values by the end of the follow-up
  • Adverse events were noted in 68 of 135 patients (see below)

OH Nielsen et al. Clin Gastroenterol Hepatol 2022; 20: 74-87. Open Access: Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis

Forty-eight studies were included in the meta-analysis comprising 6963 patients. Key findings:

  • Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% for early pregnancy loss, 9% for preterm birth, 0% for stillbirth, 8% for low birth weight, and 1% for congenital malformations.
  • These rates are comparable with those published in the general population.
  • Importantly, studies with newer biologics (eg. vedolizumab, ustekinumab) had small sample sizes. In addition, ongoing prospective multicenter registries are ongoing.

EA Spencer et al. JPGN 2021; 73: 710-716. Open Access PDF: Outcomes of Primary Ileocolic Resection for Pediatric Crohn Disease in the Biologic Era

Key findings (n=78, retrospective study, 2/3rds received biologic postoperative prophylactic therapy):

  • Endoscopic recurrence was 46% at 2 years (median time to recurrence: 10 months).
  • Histologic recurrence was present in 44% in endoscopic remission
  • At diagnosis and surgery, over a quarter met the criteria for growth failure.. Following surgery, height, weight and BMI z scores improved significantly both at 1 year and last followup