With this year’s World Cup is in full swing, it is worth noting that watching a tense-filled soccer match could have adverse consequences.
VICTORY Consortium Showing Good Results for Vedolizumab
A presentation at the 13th Congress of the European Crohn’s and Colitis Organization (ECCO, Feb 2018) indicated that Vedolizumab had similar effectiveness as anti-TNF agents for both ulcerative colitis and Crohn’s disease. This data has been presented at a recent meeting in our office, some of the GI news magazines, and also ImproveCareNow listserv.
These analyses observed that patients with UC treated with Entyvio compared to TNFα-antagonist therapy had statistically significant higher 12-month cumulative rates of mucosal healing (50% vs 42%, hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.10‑2.73) and clinical remission (54% vs 37%; HR 1.54, 95% CI 1.08‑2.18), and numerically higher steroid-free clinical remission rates (49% vs 38%; HR 1.43, 95% CI 0.79‑2.60). In CD, results reported statistically significant higher 12-month cumulative rates of mucosal healing (50% vs 41%; HR 1.67, 95% CI 1.13‑2.47), and numerically higher rates of clinical remission (38% vs 34%; HR 1.27, 95% CI 0.91‑1.78) and steroid-free clinical remission (26% vs 18%; HR 1.75, 95% CI 0.90‑3.43) compared to TNFα-antagonist therapy. These analyses were conducted by the VICTORY (Vedolizumab Health OuTComes in InflammatORY Bowel Diseases) Consortium.
My take: While the data compare anti-TNFs to vedolizumab in a “real-world setting,” the reported outcomes for anti-TNFs are lower than in other studies. Vedolizumab had the best results in those with colonic disease. Patients with Crohn’s disease with isolated small bowel disease had lower response rates.
Related study: AK Waljee et al Inflamm Bowel Dis 2018; 24: 1185-95. Using phase 3 clinical trial data with 594 subjects, the authors note that the majority of patients who will respond to vedolizumab can be identified by week 6 using a laboratory algorithm based on hemoglobin, albumin, vedolizumab level and CRP. Fformula: Hgb*Albumin*VDZ level/CRP*Weight. A cutoff of 185.96 predicted success with an AuROC of 0.75. Higher hemoglobin, higher albumin, and higher vedolizumab level, and lower CRP are associate with higher response rates.
Related blog posts:
- Summary of latest information on Vedolizumab
- GI Care for Kids Data on Vedolizumab 2017
- Latest on Vedolizumab
- Pediatric Experience with Vedolizumab | gutsandgrowth
- Vedolizumab -another new IBD treatment | gutsandgrowth
Red Top Mountain, Homestead Trail
Is There an Unlocked Gun Where Your Child Plays?
While mass shootings are occurring frequently and garner a lot of press, everyday children and adults are dying from more ‘mundane’ tragedies. To reduce some these –a recent AAP message: Is There an Unlocked Gun Where Your Child Plays?
Parents need to ask this question to protect their children.
What to Make of Median Arcuate Ligament Syndrome
A recent study (C Stiles-Shields et al. JPGN 2018; 66: 71) reports on 32 cases of median arcuate ligament syndrome (MALS) from a single center, 2011-17. To me, this is an astounding number of individuals who were operated on for this disorder. As the authors note, “MALS remains a controversial and vexing condition. 13% to 50% of healthy patients may exhibit radiographic features of celiac artery compression.”
While the authors note that pain symptoms improved significantly, they report that “comorbid psychological conditions were common, occurring in about half the sample before and after surgery.”
My take: If one finds celiac artery compression and suspects MALS, it is unclear to me if an operation is indicated and how to determine when it is indicated.
Related blog post:
Proctor Creek Trail
Which Proton Pump Inhibitor is the Most Potent?
A recent study (DY Graham, A Tansel. Clin Gastroenterol Hepatol 2018; 16: 800-808) analyzed 56 randomized trials to determine relative potency of proton pump inhibitors (PPIs) based on time in which intragastric pH was 4 or less (pH4time).
Key findings:
- Pantoprazole 20 mg was equivalent to 4.5 mg of omeprazole
- Lansoprazole 15 mg was equivalent to 13.5 mg of omeprazole
- Esomeprazole 20 mg was equivalent to 32 mg of omeprazole
- Rabeprazole 20 mg was equivalent to 36 mg of omeprazole
The authors note that peak effectiveness for PPIs was at ‘approximately 70 mg of omeprazole equivalents’. In addition, they state that twice a day dosing was more effective than increasing once a day dosing; however, three times a day dosing was not more effective than twice a day. “Dexlansoprazole, a quasi-twice-a-day formulation produced similar acid suppression to the lowest twice-daily PPI regimen and 20 mg vonoprazan once daily provided similar efficacy aas high-dose twice-daily PPI.” The authors also compare costs; generics of pantoprazole, omeprazole, and esomeprazole cost as little as $0.02-0.04 per omeprazole equivalent. Thus, 20 mg of omeprazole would be as little as 40 cents.
My take: Using the lowest effective dose of a PPI is recommended. In patients needing higher dosing or with suboptimal response to acid suppression, this data can be very helpful.
Proctor Creek Trail
The Risk of Pancreatic Cancer After Acute Pancreatitis
A recent study (J Kirkegard et al. Gastroenterol 2018; 154: 1729-36) determined that acute pancreatitis is associated with an increased risk of pancreatic cancer. This finding is based on a nationwide (Denmark), matched cohort study of all patients admitted with acute pancreatitis from 1980 to 2012. This involved 41,669 patients with acute pancreatitis and 208,340 comparison subjects.
Key finding:
- Five year pancreatic cancer risk was 0.87% compared to a risk of 0.13% in the comparison group (HR 2.02)
Limitations: While this study is based on a Danish registry, the authors note that the data had been prospectively entered and has a high validitiy.
My take: While I have not seen pancreatic cancer in the pediatric population, it is concerning that episodes of pancreatitis are likely to increase this risk for the children as well (over their lifetimes).
Mountain Laurel (?) -Pine Mountain Trail
How to Identify Dubin-Johnson Syndrome
Typically, most pediatric gastroenterologists want to remember that the gross appearance of the liver in patients with Dubin-Johnson is black as this is rumored to be a frequently asked question for board testing. Practically, though other features are important to recognize since the color of the liver is not readily evident except during surgery. As such, a recent retrospective study (T Togawa et al. J Pediatr 2018; 196: 161-7) describes 10 neonatal patients from Japan.
Key findings:
- Only 3 of the 8 patients who underwent liver biopsy had a grossly black liver
- All liver specimens showed no expression of multidrug resistance-associated protein 2 and increased expression of the bile salt export pump protein
- Homozygous or compound heterozygous pathogenic variants of ABCC2/MRP2 (ATP-binding cassette subfamily C member 2/multidrug resistance-associated protein 2) were identified in all patients
The clinical course was similar in the patients:
- Cholestasis self-limited/benign: “severe cholestasis developed in the neonatal period…reaching a maximum at 19 to 60 days. Cholestasis then decreased and disappeared at 2 to 9 months of age.” Acholic stools were common during the cholestatic phase.
- Serum AST and ALT remained consistently normal
- There was no hepatosplenomegaly and no failure to thrive
My take: Dubin-Johnson syndrome is much easier to identify with the availability of genetic panels.
Related blog post: Dubin-Johnson Syndrome
Hereditary Fructose Intolerance
A recent case series (Li H, A Diaz-Kuan, M Vos et al. Mol Genet Metab. 2018 Apr;123(4):428-432) highlights the importance of dietary history in infants with liver failure (abstract below). Congratulations to my colleague Miriam Vos one of the coauthors.
Commentary on this publication from Emory News (from Kipp Ellsworth’s twitter feed):
Babies with inherited intolerance of fructose face a risk of acute liver failure if they are fed certain widely available formulas containing fructose, pediatricians and geneticists are warning. Baby formula manufacturers should remove fructose or sucrose, or explicitly label their products to allow parents to avoid those sweeteners if necessary, the doctors say.
In a recent paper in Molecular Genetics and Metabolism, Emory geneticists Hong Li, MD, PhD and Michael Gambello, MD, PhD together with Children’s Healthcare of Atlanta pediatric hepatologist Miriam Vos, MD and colleagues report four cases of hereditary fructose intolerance (HFI), all diagnosed in early infants. All had acute liver failure that resolved when the infants switched to formula without fructose.
HFI is estimated to occur in 1 out of 20,000 live births. It comes from mutations in the aldolase B gene, resulting in an inability to metabolize fructose. Early symptoms include nausea, vomiting, abdominal pain and failure of an infant to gain weight. If unrecognized, HFI can result in liver and kidney damage, seizures or death.
HFI-related problems do not appear if an infant is being breastfed exclusively. It is normally recognized when fructose-containing solid foods, such as fruit, are introduced into the diet several months after birth. However, some baby formulas – often soy-based – contain sweeteners such as high-fructose corn syrup or sucrose (table sugar), which is made of fructose and glucose linked together. Sometimes, the label only says “sugar” instead of sucrose…
Since HFI is a treatable disease, Li urges pediatricians to consider HFI as a potential diagnosis if there is a feeding problem, elevated transaminase enzymes or jaundice (a sign of liver damage) and the infant has been fed formula containing fructose or sucrose.
Some information about a young patient’s condition can be obtained from urine carbohydrate tests, but the only way to confirm HFI is by genetic sequencing.
Abstract:
Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by aldolase B (ALDOB) deficiency resulting in an inability to metabolize fructose. The toxic accumulation of intermediate fructose-1-phosphate causes multiple metabolic disturbances, including postprandial hypoglycemia, lactic acidosis, electrolyte disturbance, and liver/kidney dysfunction. The clinical presentation varies depending on the age of exposure and the load of fructose. Some common infant formulas contain fructose in various forms, such as sucrose, a disaccharide of fructose and glucose. Exposure to formula containing fructogenic compounds is an important, but often overlooked trigger for severe metabolic disturbances in HFI. Here we report four neonates with undiagnosed HFI, all caused by the common, homozygous mutation c.448G>C (p.A150P) in ALDOB, who developed life-threatening acute liver failure due to fructose-containing formulas. These cases underscore the importance of dietary history and consideration of HFI in cases of neonatal or infantile acute liver failure for prompt diagnosis and treatment of HFI.
Related blog post: Changing Approach to Neonatal Acute Liver Failure
Chattahoochee River Near Island Ford
Interleukin 6 and Liver Disease Mortality
Briefly noted: J Remmler et al. Clin Gastroenterol Hepatol 2018; 16: 730-7. This retrospective study with 474 patients showed that blood levels of interleukin 6 were associated with mortality. In this cohort, those with levels in the lowest quartile (< 5.3 pg/mL) had zero fatalities within 1 year. In those with the highest quartile (37 pg/mL or more), had a 67.7% mortality rate within 1 year. The associated editorial (pg 630-32) notes that IL6 functions include liver regeneration, infection defense, and metabolic homeostasis. “IL6 is synthesized during inflammatory conditions…persistent activation of the IL6 pathway may have detrimental effects in the livers and in other tissues.”
Pine Mountain Trail
New Treatment for Primary Biliary Cholangitis
Another treatment is emerging for biliary cholangitis (PBC): C Corpechot et al (NEJM 2018; 378: 2171-81) shows that an inexpensive medication, bezafibrate, is effective in patients with PBC who have not responded adequately to ursodeoxycholic acid. An associated editorial (2234-35 by Elizabeth Carey) notes that this medication is not available in the U.S., though a similar medicine, fenofibrate “has shown similar efficacy” in PBC (off-label).
