Tag Archives: monitoring

Celiac Update September 2015

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A useful review (CP Kelly et al. Gastroenterol 2015; 148: 1175-86) summarizes the ‘state of the art” information regarding celiac disease presentation and management. The review notes that some expert organization consensus state that intestinal biopsy is mandatory whereas some do not under certain conditions.

According to ESPGHAN, if anti-TTG >10-fold elevated, anti-EMA positive in separate sample, and +HLA typing, then a biopsy may not be required.  For the WGO (World Gastroenterologic Organization), the exception focuses on available local resources.

The article recommends the following for monitoring:

  • Clinical evaluation -annually or if recurrent symptoms
  • Serology & Nutritional evaluation -every 3-6 months until normal, then every 1-2 years.  Common nutrient deficiencies: iron, vitamin D, vitamin B12, folate, and zinc
  • Bone density -once within first 2 years.  (Some recommend checking after 1 year on gluten free diet)
  • Liver transaminase levels & Thyroid function tests -at diagnosis, then every 1-2 years.  Autoimmune thyroid disorders are “found in approximately 15-20% of adults with celiac disease”

A second retrospective indicates that ESPGHAN criteria for avoiding biopsy in children and adolescents with high titers for anti-TTG (>10-fold) along with positive EMA, and HLA-DQ2/DQ8.are reasonable.  Here’s the abstract:

Are ESPGHAN “Biopsy-Sparing” Guidelines for Celiac Disease also Suitable for Asymptomatic Patients?

CM Trovato, et al.The American Journal of Gastroenterology , (15 September 2015) | doi:10.1038/ajg.2015.285

OBJECTIVES:

In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels ≥10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients.

METHODS:

We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh–Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers.

RESULTS:

A total of 196 patients (68.53%) had anti-tTG titers ≥10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD (“high-titer” symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic (“high-titer” asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between “high-titer” symptomatic and “high-titer” asymptomatic children (Fisher exact test, P=1.000).

CONCLUSIONS:

If confirmed in large multicenter prospective studies, the “biopsy-sparing” protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer ≥10 times ULN, positive EMA, and HLA-DQ2/DQ8.

Related blog posts:

 

 

Pediatric HCV Guidelines

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A useful recent article, ‘NASPGHAN Practice Guidelines for pediatric HCV’ (JPGN 2012; 54: 838-55) needs to be a handy reference.  However, given the rapid changes in the HCV field, it is likely that this reference will need to be updated soon to incorporate new information (eg. IL28b) as well as emerging therapies.

Highlights:

Epidemiology: 0.2% of children & 0.4% of adolescents are HCV-infected; primary mode is mother to child (vertical) transmission which occurs in 5-7% if mother not coinfected with HIV

Testing: For infants of HCV-infected mothers, check HCV antibody after 18 months or HCV RNA at younger ages.  Need two negative HCV RNAs to exclude infection (guidelines suggest checking 6 months apart).  Most individuals should be screened with antibody testing and confirmed with RNA test.

Screening for HCC (U/S, AFP): suggested only “for those with significant liver disease (ie. cirrhosis)” due to rarity of HCC in pediatric HCC.

Treatment:

  • Not if patient younger than 3 years
  • Probably Pegylated-interferon with ribavirin –references for pediatric studies indicate response rates of about 50% for genotype 1 and about 80% for types 2 & 3.
  • Who should be treated? Not always clear.  Probably those with elevated aminotransferases or progressive disease based on liver biopsy.  Possibly those with mild disease to eradicate virus.
  • Dosing: ribavirin  15/kg/day divided twice daily; weekly PEG-IFN-α-2a 180 microgram/1.73 m2 or weekly PEG-IFN-α-2b 60 microgram*m2

Treatment monitoring (Table 8):

  • CBC/diff, Hepatic panel, glucose 0, 1, 2, 4, 8, 12 weeks, then every  4-8 weeks
  • T4/TSH 0, 12, 24, 36, 48 weeks
  • Urine HCG 0, 24 weeks (if female >12 years)
  • Prothrombin, Urinalysis at week 0
  • HCV RNA 0, 24, 48, 72 weeks

Anticipatory Guidance: “no legal requirement” to disclose HCV infection in U.S.; however, CDC suggests revealing this information to sexual partners (http://www.cdc.gov/hepatitis/hcv/)

  • Avoid sharing toothbrush, shaving equipment with household contacts, unprotected sexual activity with multiple partners, tattooing/piercing
  • Do not need to screen household or casual contacts

Special issues:

  • Vaccines: HCV patients should receive all standard vaccines
  • Obesity and alcohol both can worsen the outcome
  • Fetal scalp probes and prolonged rupture of membranes but not route of delivery may increase risk of HCV transmission
  • Breastfeeding is not contraindicated but should be avoided during mastitis/bleeding

Additional related blog links:

HCV now more deadly than HIV

The cost of progress in treating Hepatitis C

Increased ferritin predicts poor response in Hepatitis C

Curing Hepatitis C without interferon

Looking for trouble

Additional references:

  • –Hepatology 2011; 54: 1433. AASLD guidelines.  See teleprevir & boceprevir as well.-http://www.aasld.org/eweb/docs/hepatitisc
  • -Hepatology 2011; 53: 1468. PEG/RBV have minimal effect on QOL/cognitive/emotional outcomes, n=114.
  • -Gastroenterology 2011; 140: 389, 450-58. HEP-C STUDY. Comb RBV (15mg/kg div BID) & PEG-2a (180mcg/1.73m2 body surface q week) is better than PEG monotherapy. 53% SVR in combo group. Neutropenia in 40% –needed to reduce dose see below). “The Combination of Ribavirin and Peginterferon Is Superior to Peginterferon and Placebo for Children and Adolescents With Chronic Hepatitis C.”
  • -Hepatology 2009; 49: 1335. Comprehensive review and guidelines
  • -J Hepatology 2010; 52: 501-07. n=107. Pediatric study. Wirth et al. Efficacy of PEG alfa-2b (1.5/g/d) & RBV (15/kg/day): Genotypes 2/3 96% SVR, genotype 1 55%.
  • -JPGN 2006; 43: 499.  Study of PEG-IFN-α-2a in children.  dose BSA m2/1.73 x 180microgm weekly x 48 weeks.  6/14 (43%) had sustained response.  all genotype 1.  Article states that IFN (3/week) + RBV has now been approved by FDA for those over 3 years

PEG-Interferon Dosing:

Dosing adjustment from hep C study in children –needed in ~40%

PEG -2a
original: 180mcg/1.73m2
1. level 1: 135 mcg, level 2: 90mcg, level 3: 45 mcg

If ANC 750-999 week 1-2: level 1 adjustment, weeks >3: no adjustment
If ANC 500-749: week 1-2: hold dose ’til >750, then level 1; weeks >3, level 1 adjustment
If ANC 250-499: week 1-2, hold until >750, then level 2 adjustment, weeks >3, then hold ’til 750, then level 1 adjustment
If ANC <250, stop drug

If PLTs 35-49K, hold til >50, then level 1
If PLTs 25-34, hold til >50, then level 2
If PLTs <25, stop drug

If Hgb <10, reduce RIBA dose by 1/2 & increase dose when hgb>10
If hgb <8.5, stop RIBA

If indirect bili >5, stop drug.  If <2.5, restart dose at one-half and if remains less than 2.5, can resume full dose after 4 weeks.

IF ALT 5-10 ULN, recheck in 1 week.  If stays high, level 1 adjustment.
IF ALT10 ULN for more than 1 week, then if drops to 5-10, level 1 but if remains >10 ULN, then stop drug.

Side effect frequency:
flu symptoms: 91%, h/a, 62%, GI symptoms 56%, injection pain 45%, muscle aches 36%, irritable 31%, fatigue 27%, rash 20%, itching 15%, anorexia 13%, trouble sleeping 11%, depression 4-12%