Changes in Latitudes and Changes in Autoimmune Liver Disease

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GJ Webb et al. Clin Gastroenterol Hepatol 2021; 19: 2587-2596. Open Access: The Epidemiology of UK Autoimmune Liver Disease Varies With Geographic Latitude

Methods: A retrospective cohort study using anonymized UK primary care records (2002-2016). All adults without a baseline diagnosis of AILD (autoimmune liver disease) were included and followed up until the first occurrence of an AILD diagnosis, death, or they left the database.

AIH, autoimmune hepatitis; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis

Key findings:

  • 1314 incident cases of PBC, 396 of PSC, and 1034 of AIH. Crude incidences were as follows: PBC, 2.47 (95% CI, 2.34–2.60); PSC, 0.74 (95% CI, 0.67–0.82); and AIH, 1.94 (95% CI, 1.83–2.06) per 100,000 per year.
  • A more northerly latitude was associated strongly with incidence of PBC: 2.16 to 4.86 from 50°N to 57°N (P = .002) and incidence of AIH: 2.00 to 3.28 (P = .003), but not incidence of PSC: 0.82 to 1.02 (P = .473)
  • After adjustments, PBC was more frequent in smokers than those who had never smoked at 3.40 (3.03–3.77) per 100,000/y and 1.96 (1.80–2.12) cases per 100,000/y; there was a lower incidence of PSC in smokers 0.47 (0.33–0.61) per 100,000/y compared with those who had never smoked 0.95 (0.83–1.07) per 100,000/y. For AIH, there was no difference between current smokers and those who had never smoked

The authors speculate in the discussion about potential reasons why latitude could correlate with disease incidence. Some potential explanations include sunlight/vitamin D metabolism (though this is at odds with the fact that those with increased skin pigmentation are NOT at increased risk), environmental exposures (related to geology, diet, air quality) or unrecognized genetic tendency based on geography.

My take: In the UK, there is an association between a more northernly latitude and both PBC and AIH.

Related blog post: Aspen Webinar 2021 Part 5 -Autoimmune Liver Disease & PSC

Figure 2

Omicron Data

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This data from NY Times shows that deaths due to COVID-19 are following a familiar pattern and spiking about 3 weeks after a spike in cases; this time the spike is being driven by omicron cases. However, this wave may in fact have lower severity per case; with this current wave, the number of reported cases is probably undercounted by a greater degree than in previous spikes due to widespread availability of home testing and the likelihood of more asymptomatic cases. Thus, it could be that the death rate per case would/will be significantly lower if/when all cases are accounted for.

Mortality Risk With Autoimmune Hepatitis

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R Sharma et al. Clin Gastroenterol Hepatol 2021; 19: 2636-2647. Open Access PDF: Increased Mortality Risk in Autoimmune Hepatitis: A Nationwide Population-Based Cohort Study With Histopathology

In this nationwide population-based cohort study in Sweden from 1969-2017 of 6,016
adults with histologically-confirmed AIH (all 18 years or older) and 28,146 matched general population, key findings:

  • 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years)
  • The 10-year cumulative incidence of death was 32.3% (95%CI [ 31.1-33.6) for AIH individuals and 14.1% (95%CI [ 13.7-14.5) for reference individuals
  • AIH individuals with cirrhosis on biopsy had a high risk of death (HR [ 4.55; 95%CI [ 3.95-5.25), while mortality risks for patients with noncirrhotic fibrosis (HR, 2.68) and inflammation without fibrosis (HR, 2.18) were similar to overall risk
  • In this cohort, 13.7% had cirrhosis at diagnosis (lower than other studies)

My take: In this study over nearly 50 years, AIH was associated with “a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension (HR, 7.55), and overlap with cholestatic liver disease.”

Related blog posts:

Course of Functional Abdominal Pain Before and During Pandemic

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C Strisciuglio et al. JPGN 2021; 73: 689-694. Overall Impact of Coronavirus Disease 2019 Outbreak in Children With Functional Abdominal Pain Disorders: Results From the First Pandemic Phase

In this multicenter, observational, international study conducted between April and July 2020 at six different referral centers, the authors studied two groups:

  1. Children diagnosed with FAPDs between October 2019 and February 2020 were enrolled and prospectively interviewed at 4 months of follow-up during the first pandemic phase (Quarantine group, n=180, mean age 14 yrs)
  2. A cohort of children diagnosed with FAPDs between October 2018 and February 2019 was used as a Control group, n=176, mean age 13 yrs)

Key findings:

  • At 4 months of follow-up, both groups had a significant reduction of children reporting >5 episodes of abdominal pain per month when compared to baseline. Quarantine group: 63.9% vs 42.2%, P < 0.001; Control group: 83.5% vs 50%, P < 0.001.
  • Overall, 57% of the Quarantine group and 63.5% of the Control group had improvement of all symptoms.

My take: This study shows that the majority of patients with functional abdominal pain have improvement (at least temporarily) and reinforce the benefit of reassurance/conservative approach for many even during the pandemic. It is possible that school closures and additional parental attention mitigated some of the improvement in the Quarantine group.

Related blog posts:

Siesta Key, FL

Bariatric Surgery Outcomes in Adolescents

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F Qureshi et al. JPGN 2021; 73: 677-683. Longitudinal Outcomes in Adolescents After Referral for Metabolic and Bariatric Surgery

Key findings (study period 2015-2020):

  • Only 22% underwent bariatric surgery (Laparoscopic sleeve gastrectomy (LSG)), mainly due to lack of interest in those referred
  • Reasons for NoLSG: 171 (62% of the NoLSG group) did not return for a 2nd visit, 28 (10%) were considered non-adherent to clinical recommendations, 14 (6%) had insurance denials, 16 (6%) had psychological contraindications including recent suicidal ideations, and 29 (11%) are still considering/pursuing LSG
  • Only 8 (2.3%) of entire cohort were self-pay
  •  LSG patients had 21% total weight loss and 22% total BMI loss at 24 months whereas NoLSG patients had 4% total weight gain and 3% BMI gain (P < 0.01)
  • LSG group had improvement in obesity-associated conditions compared to group without surgery (P < 0.01)
  • Follow-up in both groups was poor (40% for LSG group and <20% for the NoLSG group) 1 year after bariatric referral. This is of particular interest in the LSG group b/c for surgery, patients are required to agree to a 5 year f/u period (though this lacks an enforcement mechanism). The authors note some improvement in f/u coincident with recent broader adoption of telemedine

My take: This single-center found that most patients referred for consideration of bariatric surgery did not have this surgery.

 Related blog posts:

Best Allergy Articles 2021 (Part 5): Allergy Test Ordering

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In Pediatrics, supplement 3 summarizes 76 articles: Synopsis Book: Best Articles Relevant to Pediatric Allergy, Asthma and Immunology

Some of the studies that are most relevant to pediatric GI doctors I am reviewing for this blog over the next/past few days.

MT Kraft et al. Ann Allergy Asthma Immunol 2020; 125: 341-360. Review of Ordering Practices for Single-Allergen and Serum-Specific Immunoglobulin E Panel Tests for Food Allergy

In this study, the author’s examine the ordering of serum IgE food allergy tests at a single hospital in 2018. In total 12,345 tests were ordered by 400 physicians.

Key findings:

  • Allergists ordered 8986 tests, of which only 1.2% were food panels.
  • Nonallergists ordered 3368 tests, of which 37.5% were food panels.
  • Food panel ordering had dropped by 55% in absolute numbers since 2013.

In the commentary, it is noted that food serum IgE panels are not recommended “because more individuals will have detectable IgE sensitization than true symptoms” (aka false positives). “There is still a long way to go regarding educating families and nonallergist provideres on approaches to diagnosis of IgE-mediated food allergies.”

My take: This is a constant struggle. Everyday families want allergy testing on the assumption that it will be useful in treating their GI symptoms. Though dietary changes are frequently helpful in patients with GI problems, food allergy panels are likely to lead to more trouble than benefit.

Related blog posts:

Siesta Key, FL

Best of Allergy Articles 2021 -Cow’s Milk Allergy/Allergic proctocolitis (Part 4)

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In Pediatrics, supplement 3 summarizes 76 articles: Synopsis Book: Best Articles Relevant to Pediatric Allergy, Asthma and Immunology

Some of the studies that are most relevant to pediatric GI doctors I am reviewing for this blog over the next/past few days.

A Lemoine et al. Clin Exp Allergy  2021:51(9):1242-1245.  doi:10.1111/cea.13896. Rectal bleeding and cow’s milk protein-induced allergic proctocolitis: A prospective study

In this prospective cohort of infants (in France) with food protein-induced allergic proctocolitis (FPIAP) (n=76), all infants had rectal bleeding (RB) which resolved with cow’s milk protein (CMP) elimination. After the initial oral food challenge (OFC) which took place 2 to 8 weeks after resolution of rectal bleeding, OFC was repeated every 2 months.

Key findings:

  • Only 31% failed the initial OFC
  • The median age of tolerance, for those with a confirmed FPIAP based on OFC, was 6.8 months, with >75% of the cohort tolerant by 10 months of age

My take:

  1. This study shows that the majority of infants with RB probably do not have FPIAP. In those that do have FPIAP, earlier challenge is reasonable in the majority.
  2. FPIAP is generally mild and self-limited. Diagnosis is hampered by lack of validated criteria.
From Siesta Key, FL

Best Allergy Articles 2021 -Cow’s Milk Allergy (Part 3)

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In Pediatrics, supplement 3 summarizes 76 articles: Synopsis Book: Best Articles Relevant to Pediatric Allergy, Asthma and Immunology

Some of the studies that are most relevant to pediatric GI doctors I am reviewing for this blog over the next/past few days.

VM Martin et al. Pediatrics 2020; 146: e20200202. Open Access: Increased IgE-Mediated Food Allergy with Food-Protein-Induced Allergic Proctocolitis.

In this study of 153 infants with food protein-induced allergic proctocolitis (FPIAP) with documented blood in the stool, more children with FPIAP developed IgE-Food Allergy (IgE-FA) (11%) compared with healthy children.

Key points (from commentary by MT Kraft and D Stukus):

  • “Although conventional teaching is to wait until 12 months of age to reintroduce dairy to infants with FPIAP, it can likely be introduced much earlier.”
  • The diagnosis of FPIAP was associated with with an increased risk of IgE-FA, “although diagnosis was not confirmed through oral food challenges”

My take: Children with FPIAP are more likely to receive a diagnosis of IgE-FA. Prolonged restriction of milk, when no longer required, could contribute to this; in addition, some children are mislabeled as food allergic without appropriate confirmation (based on faulty testing).

Best Allergy Articles 2021 -Cow’s Milk Allergy (Part 2)

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In Pediatrics, supplement 3 summarizes 76 articles: Synopsis Book: Best Articles Relevant to Pediatric Allergy, Asthma and Immunology

Some of the studies that are most relevant to pediatric GI doctors I am reviewing for this blog over the next few days.

R Nocerino et al. J Pediatr 2021; 232: 183-191. Open Access: The Impact of Formula Choice for the Management of Pediatric Cow’s Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study

Methods: In a 36-month prospective cohort study (n=365), the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in children with oral food challenge-confirmed IgE-mediated cow’s milk allergy (CWA). 5 groups were treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF + LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid–based formula.

Key finding:

  • The use of EHCF + LGG for CMA treatment was associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

The risk ratios:  

  • 2.37 (1.46-3.86, P < .001) for rice hydrolyzed formula vs EHCF + LGG
  • 2.62 (1.63-4.22, P < .001) for soy formula vs EHCF + LGG
  • 2.31 (1.42-3.77, P < .001) for EHWF vs EHCF + LGG
  • 3.50 (2.23-5.49, P < .001) for amino acid–based formula vs EHCF + LGG

Limitations: non-blinded study, exclusion of patients with anaphylaxis-CMA