COVID Booster Advice for IBD from Dr. David Rubin (@IBDMD)

Posted on August 16, 2021 by gutsandgrowth

On Friday, our office started fielding questions regarding COVID-19 booster shots in our IBD population. Currently, I agree with the advice for patients as detailed by Dr. Rubin in the screenshots that follow. Key points:

Studies have shown that IBD patients are not at increased risk of COVID-19 infections compared to the general population.
Except for those on high-dose prednisone, it appears that our patient population with IBD does mount an adequate response to vaccination. That is, they are not considered severely immunocompromised.
In short, it is reasonable, but not a clear recommendation, to give a booster mRNA vaccine dose to patients who are receiving anti-TNF agents and those receiving immunomodulators; this is a patient choice.

Also, from CDC 8/13/21:

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.

“What is Biden Waiting For?” & COVID-19 Vaccine Effectiveness for Delta Variant

Posted on August 15, 2021 by gutsandgrowth

A good read by Don McNeil Jr: What is Biden Waiting For?

He argues that the federal government needs to do a lot more, including the use of vaccine mandates to control this pandemic.

Some excerpts:

Why is this administration so hesitant about saving American lives? And the American economy?….
The key to saving lives is vaccine. The key to reopening offices and factories is vaccine. The key to reopening schools is vaccine. The key to keeping bars and restaurants open in cold weather is vaccine. The key to travel and shopping is vaccine. Vaccine in everybody….
mRNA vaccines start waning after six months. Israel is already offering booster shots to everyone over 60. We must do the same….We are too fearful of very rare side effects…
Why in the world do we not yet have federal vaccine passports? In a land of block-chain currencies, QR code menus, encrypted texts and microchip credit cards, those little CDC-logo flashcards are just pathetic…
It’s also time to drop “religious exemptions.” No major religion — not one, from Confucianism to Catholicism — opposes vaccination…
We need to treat deliberate disinformation for what it is: a betrayal of the American public.

My take: With the emergence of the Delta variant, it will take a much higher level of vaccination/natural immunity (>95%) to control this pandemic. Vaccination is a much safer strategy than natural immunity (after infections).

Also, NEJM Quick take: Effectiveness of COVID-19 Vaccines (1:29 min). Pfizer-(BNT162b2) vaccine had 88% effectiveness against Delta variant in England after 2 doses compared to 94% for alpha variant..

Zantac 360 is Not Zantac

Posted on August 14, 2021 by gutsandgrowth

Recently the FDA has allowed Zantac to be relaunched as Zantac 360. This is well-described in a recent blog post on GoodRx: Zantac Returns to Market With a New Ingredient

While famotidine (the new ingredient in Zantac 360) acts similar to ranitidine (the old ingredient), there is no longer N-nitrosodimethylamine (NDMA) detectable which was a concern as a potential cancer risk. It comes in two different strengths (10 mg and 20 mg).

My take: In my view, it is a bad decision to allow Zantac to be relaunched with this new ingredient; this is like allowing some hot dogs to be sold as hamburgers.

Related blog posts:

Notable COVID Studies Including Persistent Post-COVID Symptoms in Children

Posted on August 13, 2021 by gutsandgrowth

COVID-19 Advice from CHOA:

D Kim et al. Clin Gastroenterol Hepatol 2021; 19: 1469-1479. Full text: Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study

Key findings:

The overall all-cause mortality in this cohort with chronic liver disease was 14.0% (n = 121 of 867), and 61.7% (n = 535) had severe COVID-19
Liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42), decompensated cirrhosis (HR 2.91) and hepatocellular carcinoma (HCC) (HR 3.31)
Related blog post: Aspen Webinar 2021: COVID-19 and the Liver

BK Elmunzer et al (>120 authors!) Clin Gastroenterol Hepatol 2021; 19: 1355-1365. Full text: Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019

Key findings:

In this cohort with 1992 patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course: GI symptoms had OR of 0.93 and liver test abnormalities had OR of 1.31 for mechanical ventilation or death.
Common GI symptoms: diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases.

Lancet Child Adolesc Health 2021. Published Online August 3, 2021. https://doi.org/10.1016/S2352-4642(21)00198-X. Open Access: Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2.

Key finding: In this prospective cohort study, 25 of 1379 (1.8%) children (5-17 yrs) had symptoms lasting at least 56 days and 4.4% had symptoms lasting more than 4 weeks.

Engineering New Treatments for Celiac Disease

Posted on August 12, 2021 by gutsandgrowth

This month’s Gastroenterology featured two new approaches for the treatment of celiac disease.

CP Kelly et al. Gastroenterol 2021; 161: 66-80. Full text: TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study

IS Pultz et al. Gastroenterol 2021; 161: 81-93. Full text: Gluten Degradation, Pharmacokinetics, Safety, and Tolerability of TAK-062, an Engineered Enzyme to Treat Celiac Disease

In the first study, Kelly et al used TAK-101 nanoparticles in Phase 1 and Phase 2a trials. In the Phase 2a trial with 33 patients, TAK-101 induced an 88% reduction in change from baseline in interferon-γ spot-forming units vs placebo (2.01 vs 17.58, P = .006). Vh:Cd deteriorated in the placebo group (−0.63, P = .002), but not in the TAK-101 group (−0.18, P = .110) Overall, TAK-101 was well tolerated and prevented gluten-induced immune activation.

Graphical abstract from **CP Kelly et al. Gastroenterol 2021; 161: 66-80**.

In the second study, Pultz et al developed TAK-062 which is a novel, computationally designed endopeptidase to break down gluten under simulated gastric conditions in vitro and in healthy participants in the phase I study. Residual gluten (collected through gastric aspiration in the phase I study) was quantified using R5 and G12 monoclonal antibody enzyme-linked immunosorbent assays. Key finding: In vitro, TAK-062 degraded more than 99% of gluten (3 g and 9 g) within 10 minutes. In the phase I study, administration of TAK-062 was well tolerated and resulted in a median gluten degradation ranging from 97% to more than 99% in complex meals containing 1–6 g gluten at 20–65 minutes postdose.

The associated editorial highlights these studies and reviews their limitations; in addition, the authors review the current non-dietary strategies (see below), pg 21-24: Full text: The Promise of Novel Therapies to Abolish Gluten Immunogenicity in Celiac Disease

From editorial, Gastroenterol 2021; 161: 21-24.

My take: These studies indicate that non-dietary treatments may be effective at some point, but not in the near future.

Related blog posts:

Paternal Exposure to IBD Medications and Neonatal Outcomes

Posted on August 11, 2021 by gutsandgrowth

COVID-19 Vaccine Effectiveness (8/10/21):

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J Meserve et al. Gastroenterol 2021; 161: 107-115. Full text: Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients With Immune-Mediated Inflammatory Diseases

Methods: The investigators used a deidentified administrative claims database (OptumLabs Data Warehouse) with a total of 7453 expectant fathers with immune-mediated diseases.

Key findings:

As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to immunosuppressives/biologics were not associated with increased risk of major congenital malformations: thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66–1.76), methotrexate (RR, 0.67; 95% CI, 0.21–1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non–TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80–3.24).
No association was observed between paternal medication exposure and risk of preterm birth or low birth weight.

Editorial, pg 24-27: S Friedman et al. Full text: Does Fatherhood Matter? Preconception Use of Biologics and Immunomodulators by Fathers With Immune-Mediated Diseases and Birth Outcomes of Their Offspring

“Regarding major congenital malformations, we believe that the results should be interpreted with caution. The numbers of these outcomes are relatively low and the statistical precision of the risk estimates should be taken into consideration.”

My take: Overall, this study is reassuring. Though it is difficult to prove these medications do not have impacts on newborns, if these effects were frequent, it would likely be evident in this type of study.

Aspen Webinar 2021 Part 8 -Neonatal Cholestasis

Posted on August 10, 2021 by gutsandgrowth

Obituary from Cincinnati Enquirer: James E. Heubi. “In lieu of flowers, memorial contributions may be made to the James Heubi Fund at Cincinnati Children’s Hospital Medical Center: http://www.cincinnatichildrens.org/donate. Please direct funds to “other” and type “James Heubi Fund.”

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This is the last of my lecture notes from this year’s Aspen Webinar 2021. This was a fantastic update by Dr. Balistreri highlighting the incredible advances in understanding the myriad of disorders which present as neonatal cholestasis.

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

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Key points:

Idiopathic neonatal hepatitis was attributed as diagnosis in ~65% of cases in 1970 but in 2021 accounts for ~10%
A lot of new disorders identified which interfere with bile flow
FXR helps prevent intrahepatic bile acid accumulation
Genetic panels (~88 genes) quickly identify most disorders, but new disorders may be missed and need whole exome
“Everybody deserves a diagnosis”

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Related blog posts:

Jessica Rutsky: Case Presentation

10 mo with jaundice and pruritus. Labs note cholestasis (D bili 7.7), normal GGT, and mild elevation of transaminases. Unremarkable ultrasound. Liver biopsy showed nonspecific changes (cholestasis, no significant fibrosis). Genetic testing led to a diagnosis of PFIC. DDx: Obstruction, Infection, Toxic (drugs), Metabolic/Genetic including Alagille, PFIC

SAVE THE DATE for next year’s conference: July 11-15, 2022 in Snowmass Village, CO

Aspen Webinar 2021 Part 7 -Cystic Fibrosis Liver Disease

Posted on August 9, 2021 by gutsandgrowth

More from Aspen Webinar 2021. This blog entry has abbreviated/summarized several presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well. Great lecture from Jim Squires.

Key points:

Cystic Fibrosis Liver Disease (CFLD) is variably defined
Risk factors include male patients, DeltaF508 mutations, meconium ileus and SERPINA1 Z allele
Two main phenotypes: Classic “Focal Biliary Cirrhosis” and Obliterative Portal Venopathy (increasingly recognized)
Intestinal microbiome and gut permeability/endotoxins may influence liver disease
Treatments: ursodeoxycholic acid may be helpful but overall evidence is low quality. Cochrane review does NOT recommend its routine use
Treatments: liver transplant (thorough review: Freeman et al. Liver Transpl 2019; 25: 640-657)
Treatments: CF Modulators: potentiators (Ivacaftor), correctors (Lumacaftor, Elexacaftor, Tezacaftor)
Treatment: Trikafta has been a game changer for CF lung disease. Its effects on the liver are not clear yet

Some of the slides:

Related blog posts:

SAVE THE DATE for next year’s conference: July 11-15, 2022 in Snowmass Village, CO

Hepatitis B: Natural History and Difficulty Treating Immunotolerant Children

Posted on August 7, 2021 by gutsandgrowth

S Mo et al. JPGN 2021; 73: 150-155. Natural History of Chronic Hepatitis B Infection Among Chinese Children and Young Adults: A Single-Center Experience

Key findings:

Of the 353 patients, there were immune-tolerant 112 (34%), HBeAg-positive immune-active 47 (14%), and inactive carrier 82 (25%). The remaining 88 patients (27%) did not fit into a particular category with 26 of 88 patients meeting the criteria for inactive carrier except for mildly elevated alanine aminotransferase
Among 179 patients followed for ≥5 years, the spontaneous seroconversion rate was 38% (from HBeAg-positive to HBeAg-negative along with anti-HBeAb positivity)

In their discussion, the authors make two key points:

“No substantial benefit from anti-viral therapy” has been evident in children in the immuno-tolerant phase (MM Jonas et al. Hepatology 2016; 63: 307-318.)
The updated AASLD guidelines “strongly recommend anti-viral therapy for HBeAg-positive pregnant women with a serum HBV DNA >200,000 IU/mL”

G Mieli-Vergani et al. JPGN 2021; 73: 156-160. Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children With Immune-Tolerant Chronic Hepatitis B

As noted above, antiviral therapy has not been shown to be effective in children who are in the immuno-tolerant phase; however, the authors of this study explored whether combination therapy could be effective in a randomized, controlled, multicenter study (n=59).

Key finding: At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group)

My take: These studies reinforce the notion that children in the immuno-tolerant phase of HBV infection do not benefit from antiviral therapy. Prevention of infection is the most promising strategy.

Related blog posts:

Confirmation Bias diagram. From Steve Stewart-Williams

Aspen Webinar 2021 Part 6 -Complications and Mgt of End-Stage liver disease

Posted on August 7, 2021 by gutsandgrowth

Key points:

Surgical options are based on primary etiology: pre-hepatic, intra-hepatic, and post-hepatic
Rex procedure is technically difficult but is preferred for pre-hepatic obstruction
Warren Shunt (distal splenorenal) and TIPS can be done for intrahepatic disease
Often difficulty in selecting patients for surgical shunting beyond refractory bleeding

Some slides: