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.
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.
“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.
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.
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
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
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
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”
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.
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. On the last day of this webinar conference, there were three more terrific lectures which addressed topics related to a a failing liver.
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:
Experience at Cincy with portal hypertension patients and shunting
Key points:
Hyperreflexia is a good indicator of stage 3 of HE
Patients with HE need to be managed in ICU
MARS is being used in some centers (even in infants)
Complications of ESLD -Kathy Campbell
This talk provided a good overview of complications including ascites, variceal bleeding, frailty & sarcopenia, and hepatopulmonary syndrome.
So sad to hear that Jim Heubi has passed away. Jim Heubi was the person I interviewed with when I was considering where to do my pediatric residency and he helped convince me to come to Cincinnati. During my fellowship, I came to admire how he was so good at everything though it was always unassuming. He was such a kind person in addition to being a mentor and role model.
More from Aspen Webinars. 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.
Dr. Mieli-Vergani presented case report of a boy with autoimmune sclerosing cholangitis and associated colitis who presented with minimal symptoms.
This case report highlights the evaluation and management of autoimmune liver disease hepatitis. Workup included autoimmune serology, GGT, celiac serology, calprotectin, and ultrasonography. EGD-Colonoscopy was prompted by elevated calprotectin. MRCP was prompted by elevated GGT (GGT were normal at the time of biopsy and MRCP) and liver biopsy findings.
“My message is that MRCP and colonoscopy should be done in all cases of autoimmune liver disease in children and adolescents, irrespective of calprotectin levels or elevated GGT and biliary changes on histology, as both IBD and sclerosing cholangitis can be present without any of the classical symptoms and signs. Only by doing this it is possible to reach an early diagnosis which is essential for early treatment and for a good outcome.”
Outcome data indicate that 11 of 83 (13%, 5 AIH, 6 ASC)) required transplantation. “I have shown our long-term outcome data not to stress the number of patients who have required transplantation, but the number of patients who are well and have a normal life after over 14 years of follow-up. This can be only achieved if one thinks of autoimmune liver disease even if the child appears to have something non-specific, initiating correct treatment for the liver, and the gut if there is bowel disease, as soon as possible. At the beginning, treatment should be monitored very closely (at least weekly), to be able to decrease the dose of steroids swiftly, introduce azathioprine if needed, and avoid side affects.”
Key points:
Budesonide is not a good substitute for prednisone in autoimmune hepatitis
Mycophenolate is frequently used as a 2nd line agent
Consider calprotectin in patients with autoimmune liver disease to screen for IBD (though calprotectin can be falsely-negative)
Consider followup liver biopsy after normalization of liver enzymes for ~3 yrs (when consideration of stopping medications)
Recommends MRCP for all patients with AIH
Some slides:
Key points:
Better understanding of immune basis of PSC is developing
MMP-7 appears to help differentiate PSC/ASC from AIH
Small duct PSC is more common in children
SCOPE index can help predict outcomes
Treatment: no clear benefit of vancomycin, ursodeoxycholic acid compared to placebo but need for randomized controlled study
Several studies of new agents for PSC in adults are ongoing, including nor-UDCA, cilofexor, bezafibrate
Vedolizumab does not appear to be effective for PSC
Child with FTT, elevated LFTs, sporadic mild hypoglycemia, and neurologic symptoms. DDx: congenital disorders of glycosylation (CDG), mitochondrial d/o, peroxisomal d/o, urea cycle d/o and lysosomal d/o. Diagnosis was made after liver biopsy and whole exome sequencing (which showed PMM2 mutations). Diagnosis of most CDG can be made by serum transferrin isoforms. Discussion among many participants noted that liver biopsy often not needed in age of genetic testing.
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. An excellent review from Dr. Sokol.
What’s New with IFALD Ronald Sokol
Key points:
Biliary cirrhosis related to parenteral nutrition has been the major indication for small bowel transplantation/multi-visceral transplantation. IFALD presentations: Steatosis, biliary tract disease and cholestasis
Conjugated bilirubin >2.5 had RR 22.5 for mortality (prior to availability of intestinal transplantation)
Even after weaning off PN, studies have shown long-lasting fibrosis and steatosis in more than 40% of patients (>8 yrs off PN)
Intestinal microbiome is altered in patients with IFALD
Puder M et al. (Ann Surg 2009; 250: 395) showed that fish oil (at lower doses) was associated with improvement/resolution of parenteral nutrition associated cholestasis (PNAC)
Lipid reduction also is associated with cholestasis resolution
Caution with Fish oil (omegaven): 1. Does not prevent hepatic fibrosis progression 2. Reduction of lipid doses can have negative effects on brain growth
Lipid management has been crucial in reducing the number of children needing intestinal transplantation
Some of the slides:
IBAT Inhibitors Frederick Suchy
Key points:
IBAT inhibitors block intestinal absorption of bile acids/disrupt enterohepatic circulation; this leads to augmented bile acid excretion in stools
IBAT inhibitors may reduce liver damage in the setting of cholestasis/accumulation of toxic bile acids
Potential diseases for IBAT inhibitors include Alagille syndrome and PFIC
Van Wessel et al (J Hepatol 2020; 73: 84-93) correlated survival with PFIC1/PFIC2 with bile acid levels and showed improvement in survival in those with surgical biliary diversion
Goals for IBAT inhibitor trials: improvement in pruritus, bile acids, reduced ALT, hepatic fibrosis, HCC and need for liver transplantation
Marixibat is available for use as an FDA approved breakthrough medication for Alagille and PFIC2 in pediatric patients older than 1 year
Odexibat is designated as an orphan drug for Alagille, PFIC, PBC, and biliary atresia
Safety appears good with IBAT inhibitors. Fat soluble vitamin monitoring is needed
Case report: Alejandro Velez Lopez
3 yo presented with fatigue and jaundice, 3 weeks after COVID-19 infection. She was not taking any medications. Labs: ALT 939, AST 1321, T bili 5.5, D bili 0.9, INR 2, Plts 174, Hgb 12.8, LDH 1297. remained positive for SARS-CoV2 by PCR. Acetaminophen -no exposure. Evaluation: LKM 1:1280. Neg ANA, NL Ferritin, NL sIL2r, Other viral studies negative, NL IgG. Developed encephalopathy with NH4 317, INR peaked at 2.8. Treated with steroids, rifaximin and lactulose. Liver biopsy showed sub-massive necrosis and fibrosis (indicative of autoimmune hepatitis, likely triggered or exacerbated by COVID-19). Patient responded to medical therapy and did not require liver transplantation.
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. Another great lecture from Dr. Suchy.
IBAT Inhibitors Frederick Suchy
Key points:
IBAT inhibitors block intestinal absorption of bile acids/disrupt enterohepatic circulation; this leads to augmented bile acid excretion in stools
IBAT inhibitors may reduce liver damage in the setting of cholestasis/accumulation of toxic bile acids
Potential diseases for IBAT inhibitors include Alagille syndrome and PFIC
Van Wessel et al (J Hepatol 2020; 73: 84-93) correlated survival with PFIC1/PFIC2 with bile acid levels and showed improvement in survival in those with surgical biliary diversion
Goals for IBAT inhibitor trials: improvement in pruritus, bile acids, reduced ALT, hepatic fibrosis, HCC and need for liver transplantation
Marixibat is available for use as an FDA approved breakthrough medication for Alagille and PFIC2 in pediatric patients older than 1 year
Odexibat is designated as an orphan drug for Alagille, PFIC, PBC, and biliary atresia
Safety appears good with IBAT inhibitors. Fat soluble vitamin monitoring is needed
3 yo presented with fatigue and jaundice, 3 weeks after COVID-19 infection. She was not taking any medications. Labs: ALT 939, AST 1321, T bili 5.5, D bili 0.9, INR 2, Plts 174, Hgb 12.8, LDH 1297. remained positive for SARS-CoV2 by PCR. Acetaminophen -no exposure. Evaluation: LKM 1:1280. Neg ANA, NL Ferritin, NL sIL2r, Other viral studies negative, NL IgG. Developed encephalopathy with NH4 317, INR peaked at 2.8. Treated with steroids, rifaximin and lactulose. Liver biopsy showed sub-massive necrosis and fibrosis (indicative of autoimmune hepatitis, likely triggered or exacerbated by COVID-19). Patient responded to medical therapy and did not require liver transplantation.
gutsandgrowth 