Category Archives: Pediatric Gastroenterology Liver Disease

When Will MRI Obviate the Need for a Liver Biopsy in Pediatric NAFLD?

Posted on by

A recent study (JB Schwimmer et al. Hepatology 2015; 1887-95, editorial Vos MB, pages 1779-80) examines the accuracy of magnetic resonance imaging (MRI) compared with liver histology in children with nonalcoholic fatty liver disease.

This prospective validation study enrolled 174 children with a mean age of 14 years.  The MRI estimated the liver proton density fat fraction (PDFF).

Key findings:

  • Liver MRI-PDFF correlated with steatosis grade; the correlation was particularly strong at high and low end values.  Thus, a very low MRI-PDFF was highly likely to predict a steatosis grade 0 or 1 while a very high value corresponded to high steatosis levels.
  • Liver MRI-PDFF was weaker in children with stage 2-4 fibrosis than in children with no fibrosis

The editorial notes that this study “is one of hundreds now published in the literature on MRI and NAFLD…The superiority of MR-based methods…over ultrasound is clear.  The question is why are we still ordering abdominal ultrasounds to diagnose NAFLD in children?”  The barriers for usage of MRI include cost, potential sedation, and nonuniform methods for MRI usage.

The paper conclude that “MRI is not yet sufficient to replace liver biopsy in children.”  The editorial also indicates that the MRI era is fast approaching but not viable today.

Take-home point: Due to the huge numbers of patients with pediatric NAFLD, MRI remains a terrific area for research but remains problematic in clinical practice.  Given the expense of MRI, until its use can reduce liver biopsies or improve management, its role is likely to remain limited.

Turner Field

Turner Field

 

Understanding the Reasons for Abnormal Liver Enzymes in Pediatric Inflammatory Bowel Disease

Posted on by

A recent large single center study (Pusateri AJ et al. JPGN 2015; 60: 592-97) provides some very practical information regarding elevated liver enzymes in the setting of inflammatory bowel disease (IBD).  Because there are some serious liver diseases associated with IBD and due to the potential for liver toxicity from many of the medications, bumps in liver enzymes need to be carefully considered.

This retrospective study with 514 patients indicates that 77% of these elevations are transient. Table 1 lists the definitions (chronicity, severity) and patterns that were analyzed.  Transient elevations were broken down into brief (<30 days), prolonged <180 days, chronic >180 days and either intermittent or continuously abnormal. The three types were the following:

  • Hepatic: elevated ALT and/or AST; normal alkaline phosphatase (AP), GGT, and direct bilirubin (DB)
  • Cholestatic: elevated AP, GGT, and/or DB; normal ALT and AST
  • Mixed

Severity or degree was classified as follows:

  • 1 –peak liver enzyme 0-1 x ULN
  • 2 –peak liver enzyme >1-2 x ULN
  • 3 –peak liver enzyme >2-4 x ULN
  • 4 –peak liver enzyme >4 x ULN

Key findings:

  • 219 of 514 patients had 1 or more episode of abnormal liver enzymes; five patients with preexisting liver disease were excluded from the analysis.
  • Of 214 patients (152 with Crohn’s disease [CD], 62 with Ulcerative colitis [UC]) with abnormalities, 69% had a hepatitic pattern, 8% had a cholestatic pattern, and 23% had a mixed pattern. There was no association between the pattern and the final diagnosis (eg. idiopathic vs defined etiology)
  • Only 128 had adequate data to assess chronicity.  In this group, 77% had transient elevations (CD 75%, UC 80%)
  • 87% of elevations were considered idiopathic.  65% of patients with idiopathic elevation had levels < 2 times ULN.
  • Among patients with levels <2 times ULN, 95.3% had an idiopathic etiology.
  • Among patients with levels >4 times ULN, 63% had a benign idiopathic etiology
  • Figure 1 provides a pie chart of diagnoses.  Among the 12.6% with a specific etiology for elevated liver tests, drug toxicity was the most common reason: 51.9% were considered due to 6-MP therapy, 3.7% due to methotrexate, 3.7% due to acetaminophen.
  • Other identified causes among the 12.6% with a defined etiology included NAFLD in 11.1%, infections (CMV,EBV, Histoplasmosis) in 14.8%, cholelithiasis in 3.7%, autoimmune hepatitis in 3.7%, primary sclerosing cholangitis/overlap in 3.7%, and vascular malformation in 3.7%.

As with any retrospective study, there are a number of limitations, especially underdiagnosis given a lack of uniform approach to evaluation.  That being said, all patients had a minimum follow-up of at least nine months and most patients with prolonged liver enzyme elevation would have been examined closely.

Bottomline: This study provides reassurance that liver enzyme elevations are common in children with IBD, occurring in >40% of patients over 3 years at this center; most often these elevations are benign and transient.

Related blog posts:

Clinical Features of Byler Disease

Posted on by

A recent article (Morris AL, et al. JPGN 2015; 60: 460-6) provides a detailed analysis of six cases of Byler disease during their first two years of life.  These cases were strictly defined and defined by homozygous c.923G>T mutation of ATP8b1.

Presenting features:

  • 2 with newborn direct hyperbilirubinemia
  • 2 with complications of coagulopathy. “Bleeding diathesis is a particular issue in the Amish community where home delivery is common and vitamin K may not be administered perinatally.”
  • 1 with failure to thrive and rickets
  • 1 was a sibling identified with newborn genetic testing

Key features:

  • Intensive fat-soluble vitamin supplementation was needed. “Vitamin K deficiency can be lethal.”
  • Poor growth was frequent (Figure 2): “growth trajectories were generally at the low end of percentiles and did not reflect parental size.” It was “typically responsive to supplementation with medium-chain triglyceride-based formula. and/or use of 30 cal per ounce formulae.”
  • Elevated serum bile acids and low normal GGT (Υ-glutamyltranspeptidase)
  • Diarrhea was commonly reported
  • Intractable pruritus in 4 of 6 children which developed between 6-12 months of age;  in two patients rifampin therapy was effective.
  • Partial external biliary diversion was used in 4 children during 2nd year of life; there was a “generally favorable response to PEBD.”
  • There were not issues noted with portal hypertension

Bottomline: This report shares some practical experience with this rare disorder.

Related blog posts:

Reaching Consensus on Bariatric Intervention in Children and Adolescents

Posted on by

A recent medical position paper (Nobili V, et al. JPGN 2015; 60: 550-61) provides guidance for bariatric surgery intervention in children and adolescents with and without nonalcoholic fatty liver disease (NAFLD).

While the authors acknowledge that bariatric surgery can “dramatically reduce the risk of adulthood obesity and obesity-related diseases,” they advocate its use in adolescents with the following:

  • BMI >40 kg/m-squared with severe comorbidities: type 2 diabetes mellitus, moderate-to-severe sleep apnea, pseudotumor cerebri, or NASH with advanced fibrosis (ISHAK score >1)
  • BMI >50 kg/m-squared with mild comorbidities: hypertension, dyslipidemia, psychological distress, gastroesophageal reflux, anthropathies, NASH, impairment in activities of daily living, mild obstructive sleep apnea, panniculitis, chronic venous insufficiency, urinary incontinence
  • Additional criteria: have attained 95% of adult stature, failed behavioral/medical treatments, psychological evaluation perioperatively, avoid pregnancy for 1 year after surgery, will adhere to nutritional guidelines after surgery, informed assent from teenager (along with parental consent)

Key points:

  • “There is a lack of randomized controlled trials examining the effects of bariatric surgery on NAFLD or NASH.”  In Table 3, the authors provide a summary of 16 previous studies/outcomes; though none of the studies enrolled more than 60 patients.
  • In an adult prospective study with 381 patients (Mathurin P et al. Gastroenterol 2009; 137: 532-40), there was a significant decline in the severity/prevalence of steatosis and resolution of NASH at 1 and 5 years.
  • Bariatric surgery, in adult studies, have improved diabetes, insulin resistance, hypertension, and dyslipidemia.
  • Patients who have “undergone bariatric surgery show higher suicide rates than the general population.”  Psychological evaluation should be integrated with surgical decision.
  • Type of surgery: Roux-en-Y Gastric Bypass (RYGB) is favored by the authors; they also discuss studies with Laparoscopic Adjustable Gastric Banding (LAGB).  “RYGB and LAGB are the 2 main surgical procedures that have been used in pediatric obesity.  RYGB is considered a safe and effective option for adolescents with extreme obesity, as long as appropriate long-term follow-up is provided. LAGB has not been approved by Food and Drug Administration for use in adolescents, and there should be considered investigational only.”

It is interesting that the authors are so deferential to the Food and Drug Administration.  It is clear from their position paper that LAGB has similar evidence supporting its use in adolescents as RYGB.  They even note that it has potential for reversibility and “an excellent safety profile with a lower risk of postoperative vitamin deficiencies when compared with biliopancreatic diversion and RYGB.”

Bottomline: Given the continuation of the obesity epidemic, additional pediatric medical expertise will be needed to help evaluate adolescents for bariatric surgery and to follow them postoperatively.

Related blog posts:

Weight Loss Improves NASH

Posted on by

A recent study (http://dx.doi.org/10.1053/j.gastro.2015.04.005) helps confirm the notion that the most effective therapy for nonalcoholic steatohepatitis is weight loss. (From Rohit Kohli twitter feed).

Abstract:

Background & Aims

It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis (NASH). We examined the association between the magnitude of weight loss through lifestyle modifications and changes in histologic features of NASH.

Methods

We conducted a prospective study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks, from June 2009 through May 2013, at a tertiary medical center in Havana, Cuba. Liver biopsies were collected when the study began and at week 52 of the diet, and analyzed histologically.

Results

Paired liver biopsies were available from 261 patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72 (25%) achieved resolution of steatohepatitis, 38 (47%) had reductions in NAFLD activity scores (NAS), and 56 (19%) had regression of fibrosis. At week 52, 88 subjects (30%) had lost 5% or more of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histological parameters (odds ratios, 1.1–2.0;P<.01). A higher proportion of subjects with 5% weight loss or more had NASH resolution (51/88, 58%) and a 2-pt reduction in NAS (72/88, 82%) than subjects that lost less than 5% of their weight (P<.001). All patients who lost 10% of their weight or more had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis. All patients who lost 7%−10% of their weight and had few risk factors also had reduced NAS. In patients with baseline characteristics that included female sex, body mass index ≥35, fasting glucose >5.5 mmol/L, and many ballooned cells, NAS scores decreased significantly with weight reductions of 10% or more.

Conclusions

A greater extent of weight loss, induced by lifestyle changes, is associated with the level of improvement in histologic features of NASH. The highest rates of NAS reduction, NASH resolution, and fibrosis regression occurred in patients with weight losses of 10% or more.

Stool Color Cards -Not Flashy but Effective

Posted on by

A recent report (Gu YH et al J Pediatr 2015; 166: 897-902) shows the cumulative experience of 19 years of using stool color cards to detect biliary atresia.  Cards were distributed to all pregnant women (Tochigi Prefecture, Japan) prior to or during the postnatal one-month health check.

Key findings:

  • 34 patients detected among 313,230 live births. Reported sensitivity: 76.5% and specificity 99.9%.
  • Mean age for performance of Kasai was 59.7 days.
  • Improved long-term retention of native liver: 88% at 5 years, 77% at 10 years, and 49% at 15 years.

Limitation: Children in Western countries have had lower success rates following Kasai procedure, so it is unclear whether stool cards would be as effective in different regions.

Take-home message: Detecting biliary atresia earlier will improve outcomes.  Stool color cards should be an easy low-tech option.  Other options would include stool color apps and checking bloodwork.

Image below from Screenshot from John Pohl’s twitter feed:

Embedded image permalink

Related blog posts:

 

 

Fatty Liver at Birth

Posted on by

A provocative study (Patel KR, White FV, Deutsh GH. JPGN 2015; 60: 152-58) shows that hepatic steatosis/fatty liver is prevalent at birth in at-risk stillborns.

The authors retrospectively examined autospy results from 33 stillborns (20-40 weeks) delivered to women with diabetes (pregestational or gestational) along with 48 age-matched controls.  The majority of women (54%) were African American women; 27% were white and 9% were hispanic.

Key findings:

  • Hepatic steatosis was common and severe in the stillborns of diabetic women.  Prevalence: 78.8% (26/33) compared with 16.6% (8/48) of controls.
  • No direct correlation was identified between steatosis and glycemic control.

Whether nonalcoholic fatty liver disease (NAFLD) begins at birth is not known and what happens to the fat in newborns with hepatic steatosis is not clear.  This study indicates that maternal diabetes may increase the risk of NAFLD.

Related blog posts:

Bile Acid Therapy for BAAT

Posted on by

In a previous post (From theory to bedside practice | gutsandgrowth), I reviewed an article which described the diagnosis of a rare inborn error of bile acid metabolism –bile acid CoA:amino acid N-acyl transferase (BAAT).  A new report (Hepatology 2015; 61: 268-74) describes treatment and outcome in five patients with BAAT (I am thankful for acronyms!).

Treatment with 15 mg/kg of glycocholic acid (GCA) improved duodenal bile acid concentrations (to 23.3 ± 19.1 mmol/L).  Patients also received oral vitamin D2 (1000 IU/kg) and tocopherol (100 IU/kg).  With the combination of GCA and fat soluble vitamin provision, there was improvement in growth (3/3 prepubertal patients) and in fat-soluble vitamin absorption.

Bottomline: In patients with neonatal cholestasis growth failure, or fat-soluble vitamin deficiencies, identification of BAAT with fast atom bombardment mass spectrometry allows for institution of GCA which is efficacious and safe.

Also noted: FDA approves Cholbam to treat rare bile acid synthesis disorders FDA announcement 3/17/15, an excerpt: the first FDA approved treatment for pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders (including Zellweger spectrum disorders). Patients with these rare, genetic, metabolic conditions exhibit manifestations of liver disease, steatorrhea (presence of fat in the stool) and complications from decreased fat-soluble vitamin absorption. Individuals with these rare disorders lack the enzymes needed to synthesize cholic acid, a primary bile acid normally produced in the liver from cholesterol. The absence of cholic acid in these patients leads to reduced bile flow, accumulation of potentially toxic bile acid intermediates in the liver (cholestasis), and malabsorption of fats and fat-soluble vitamins in the diet. If untreated, patients fail to grow and can develop life-threatening liver injury. Cholbam is approved as an oral treatment for children aged three weeks and older, and adults.

Two Shorts -Minimal Hepatic Encephalopathy and Fish Oil Protection

Posted on by

Briefly noted: JPGN 2014; 59: 689-94.  In this study, the authors took a consecutive sample of 13  children (ages 4-18 years) with non cirrhotic extrahepatic portal vein portal vein obstruction (EHPVO).  Three tests (fasting ammonia, quantified EEG, a psychometric battery) identified that minimal hepatic encephalopathy (MHE) affects approximately 50% of children with EHPVO.

Also: JPGN 2014; 59: 708-13.  In this study in 7-day old rabbits, those who receive TPN with fish oil-based lipid emulsion had protection against biochemical and liver histologic damage in comparison to rabbits who received TPN with soybean oil. Given the lack of head-to-head randomized studies in infants, this study provides some important evidence of fish oil benefit compared with standardized soybean lipid emulsion.

Related blog posts:

Improving MRI for NAFLD

Posted on by

From MedicalNewsToday – a summary of a recent Hepatology study by Jeffrey B. Schwimmer, MD and colleagues.

Excerpts from http://www.medicalnewstoday.com/releases/289088.php along with image.

“In this study, the researchers compared a new MRI technique to the standard liver biopsy method of assessing fat in the liver. To do this, the team enrolled 174 children who were having liver biopsies for clinical care. For each patient, the team performed both MRI-estimated PDFF and compared the results to the standard pathology method of measuring fat on a liver biopsy.”

Screenshot from MedicalNews

Screenshot from MedicalNewsToday

“The team found a strong correlation between the amount of liver fat as measured by the new MRI technique and the grade of liver fat determined by pathology. This is an important step towards being able to use this technology for patients. Notably, the correlation was influenced by both the patient’s gender and the amount of scar tissue in the liver. The correlation between the two techniques was strongest in females and in children with minimal scar tissue.”

“Depending on how the new MRI technology is used, it could correctly classify between 65 and 90 percent of children as having or not having fatty liver tissue.”

“… However, further refinements will be needed before this or any other MRI technique can be used to diagnose NAFLD in an individual child.“