Tag Archives: steroids

Autoimmune Hepatitis: Safety of Low Dose Steroids and Utility of Aminotransferases

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K Manwani et al. JPGN 2022; 75: 252-256. Long-Term Growth in Children and Young People with Autoimmune Liver Disease Treated with Daily Steroids

This retrospective study of patients (n=74) diagnosed with autoimmune hepatitis (AH) prior to 16 years of age examined the safety of low dose steroids. Median age of patients with 12.8 yrs and median followup was 12.6 years. Typically, after induction, patients were tapered over ~2 months to 5 mg per day (& 2.5 mg per day if <12 years). Key findings:

  • Growth of patients with AILD on a daily maintenance dose of steroids remains stable and within normal range during long-term follow up.  At all time-points, the mean z-scores for weight, height and BMI were within the normal range, indicating normal nutritional status. 
  • Small, daily doses are effective in maintaining disease control and minimize the need for high-dose steroid pulses during relapses.
  • In this cohort, there were 14 patients in which prednisolone was utilized as monotherapy; the majority received cotherapy with azathioprine (n=44), mycophenolate (n=12); triple-therapy was utilized tacrolimus (n=4).
  • Prednisolone was stopped in 17 patients (23%) after a median time of 9.5 years (range 3 years-14 years)

M Biewenga et al. Clin Gastroenterol Hepatol 2022; 20: 1776-1783. Open access! Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

In this multicenter cohort study (n=301), it was shown that higher aminotransferases during treatment were independent of baseline risk factors associated with liver transplantation–free survival in patients with AIH type 1. Median followup was 99 months. Key finding:

  • During follow-up, 15 patients required liver transplantation and 33 patients died
  • In multivariate analysis AST at 12 months (HR, 2.13; P < .001) was predictive for survival independent of age, AST at diagnosis and cirrhosis, while IgG was not associated with survival (HR, 1.30; P = .53)
  • There was a trend toward a worse survival in patients with mildly elevated aminotransferases (1–1.5× upper limit of normal) compared with patients with normal aminotransferases (P = .097)

My take: Normalization of AST (aminotransferases), especially during the first year of treatment, is associated with better long-term outcomes. The study by Manwani et al suggest that long-term low dose steroids are associated with low risks.

Also: Y Li et al.Hepatology 2022; 76: 564-575. Genome-wide meta-analysis identifies susceptibility loci for autoimmune hepatitis type 1 This study with 1622 Chinese patients identified two novel loci (CD28/CTLA4/ICOS and SYNPR) and may provide potential targets for additional treatments.

Related blog posts:

AST Values and Cumulative Live Transplant-Free Survival

Standardizing the Care of Children Receiving Chronic Glucocorticoid Therapy

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A recent study (ML Basiaga et al. J Pediatr 2016; 179: 226-32) highlights the large variation in care for 701 children receiving  steroids (for at least 15 days) at a leading children’s hospital (CHOP).  I think, given the fact that this is a retrospective study and the huge variation in steroid exposure, the message regarding variation should not be taken that seriously.  But, the article does suggest that in children with chronic glucocorticoid therapy, several measures should be considered:

  • Bone health -particularly Vitamin D (25-OH) levels
  • Immunity -particularly assuring pneumococcal and influenza vaccines
  • Lipid screening
  • Stress steroid plan.  The authors indicate that the endocrinology society recommendations have included instructing parents in intramuscular hydrocortisone in case of vomiting or severe stress.

My take: Having a standard approach to an at-risk group makes sense, however, “whether implementation of preventive care guidelines improves outcomes in children” is not known.

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Acute Liver Failure –Is There a Role for Steroids?

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The title is not a simple question.

Some who support the use of steroids (for acute liver failure) should remember Galen’s assertion about a different treatment, circa 100 AD:   “All who drink of this remedy recover in a short time except those whom it does not help, who all die. It is obvious, therefore, that it fails only in incurable cases.”

Two recent publications offer conflicting advice about steroids for acute liver failure (ALF):

  • Hepatology 2014; 59: 612-21.
  • J Pediatr 2014; 164: 407-409.

The first study involved a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF from patients (n=361) prospectively enrolled in the ALF Study Group between 1998-2007.

  • Autoimmune, n=66, mean age 46 years
  • Indeterminate, n=164, mean age 39 years
  • Drug-induced, n=131, mean age 44 years

Outcomes:  Steroid use was associated with increased spontaneous survival (35% vs 23%) but this benefit did not persist with multivariate analysis.  In addition, steroid use was associated with lower survival in patients with the highest MELD scores. Furthermore, the authors discount the possibility of selection bias, noting that INR was higher in the no-steroid group.

In contrast, the second article, a case presentation/pediatric grand rounds article, states that “in our experience over the past decade, more than one-half of the children (56%) presenting with indeterminate acute hepatitis or ALF (after being evaluated) comprehensively …had a markedly elevated sIL-2R level (>5000 U/mL) concerning for immune activation but never fulfilling diagnostic criteria for HLH [hemophagocytic lymphohistiocytosis] during their course.”

“Notably, of the patients presenting with elevation of sIL-2R to >5000 U/mL, most who survived with their native liver had received treatment with steroids.” (JPGN 2013; 56: 311-5.) “We propose that children presenting with indeterminate, progressive hepatitis or indeterminate ALF are candidates for prompt initiation of anti-inflammatory therapy when there is concomitant evidence of immune activation.”

In patients with ALF, part of the evaluation needs to include sIL-2R. Other assessments for immune dysregulation would include serum triglycerides, ferritin, “CD107a expression, perforin/granzyme B protein expression, and assessment for macrophage activation (soluble CD163).”

Bottomline: If HLH criteria are not met, but patients have marked elevation of sIL-2R (>5000 U/mL), empiric corticosteroids need to be considered. Perhaps there is a window of opportunity (before a patient develops a high MELD score).  At the same time, we need to acknowledge that our knowledge base remains incomplete and it is unclear whether this will improve the outcome.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.

Challenging assumptions

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While this topic is not directly related to pediatrics or pediatric gastroenterology, I found a recent article regarding the treatment of back pain with steroids interesting.  This study challenges a treatment algorithm of using steroids to relieve inflammation triggering back pain.  The investigators showed that steroids per se are not more beneficial then saline in improving back pain.  Here is an excerpt from the NY Times, http://t.co/RF5O78odWe:

Questioning Steroid Shots for Back Pain

By NICHOLAS BAKALAR

Injecting steroids into the area around the spinal cord, known as an epidural, is the most commonly used treatment for back pain, but a new review of studies suggests that injecting any liquid, even plain saline solution, works just as well.

Researchers pooled the results of 43 studies involving more than 3,600 patients who got various kinds of injections for back pain. As they expected, they found some evidence that epidural steroid injections provided more relief than steroid injections into the muscles.

But the study, published online in Anesthesiology, also found that there was little difference between the amount of relief provided by steroidal and nonsteroidal epidural injections.

The researchers suggest that any liquid injected epidurally can help reduce inflammation, enhance blood flow to the nerves and clean out scar tissue.

Comment: There are inherently many limitations in pooling 43 studies and trying to reach a definitive conclusion.  Nevertheless, this study challenges some long-term treatment approaches.