Category Archives: Pediatric Gastroenterology Liver Disease

Liver Briefs May 2017

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Briefly noted:

O Jeanniard-Malet et al. JPGN 2017; 64: 524-7. This survey of 28 centers in France assessed clinical practice with regard to primary prophylaxis in portal hypertension. More than 75% use endoscopy to screen for varices in patients with chronic liver conditions. “In cases of grade 2 varices with red marks and grade 3 varices >90% of centres perform sclerotherapy or endoscopic variceal ligation.”

Y-D Ren et al. Hepatology 2017; 65: 1765-8. FMT for chronic HBV? This small study with 5 patients who received fecal microbiota transplantation in an effort to clear HBeAg.  There were 13 controls.  Patients in both group received either ongoing entecavir or tenofovir antiviral therapy (& had received for at least 3 years). FMT was given every 4 weeks (1 to 7 treatments). HBeAg declined gradually after each round.  Three patients in the FMT arm cleared HBeAg compared with none in the control arm.  Two of the three cleared HBeAg after on FMT and the third after two rounds of FMT.

Y Sun et al. Hepatology 2017; 65: 1438-50.  In this report, the authors propose to augment the liver biopsy classification in patients with Hepatitis B.  Their goal is to provide more information about dynamic changes regarding fibrosis using three terms:

  • Predominantly progressive: thick/broad/loose/pale septa with inflammation
  • Predominantly regressive: delicate/thin/dense/splitting septa
  • Indeteminate

Using this new designation, they characterized 71 paired liver biopsies before and after entecavir for 78 weeks.  Before treatment: 58%, 29%, and 13% for progressive, regressive and indeterminate; after treatment: 11%, 11%, and 78% respectively.

Rodin Museum, Gates of Hell

 

Mauriac Syndrome (Glycogenic Hepatopathy)

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A case report (T Malikowski et al. Gastroenterol 2017; 152: 947-49) provides some insight into a fairly common problem –elevated liver tests in the setting of poorly controlled type 1 diabetes mellitus.  This 18-year-old had presented with a glucose of 497 mg/dL, elevated lactate, aspartate aminotransferase 257 U/L, and alanine aminotransferase 178 U/L.

The authors note that Mauriac syndrome “occurs in young patients as a result of poorly controlled type 1 diabetes mellitus.”  It may result in growth retardation, pubertal delay, and cushingoid features.

“Glycogenic hepatopathy is a underrecognized complication of Mauriac syndrome that presents with abdominal pain, nausea, vomiting, elevated serum transaminases, elevated plasma lactate levels, and hepatomegaly  The pathogenesis stems from an accumulation of glycogen in the liver…The diagnosis…is made …when all other causes of liver disease have been excluded…When glucose control is achieved, prognosis is excellent.”

My take: There are many potential reasons for elevated liver enzymes associated with type 1 diabetes mellitus, including celiac disease, and autoimmune hepatitis.  However, familiarity with glycogenic hepatopathy helps with pattern recognition and helps explain the frequent concurrence of liver disease with poorly controlled type 1 diabetes mellitus.

Liver Problems with Inflammatory Bowel Disease

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A recent review (Full text: LJ Saubermann et al. JPGN 2017; 64: 639-52)  discusses the hepatic issues and complications associated with inflammatory bowel disease.

Key topics:

  • Primary Sclerosing Cholangitis (PSC)
  • Autoimmune Hepatitis (AIH)
  • Autoimmune Sclerosing Cholangitis (ASC)
  • Portal Venous Thrombosis/hypercoagulability
  • Cholelithiasis (more common in Crohn’s disease if diseased terminal ileum)
  • Viral hepatitis
  • Drug-Induced Liver Disease
  • Fatty Liver disease

Many of these topics have been discussed previously on this blog.  A couple of pointers in this review:

PSC:

  • Greater risk of colorectal carcinoma
  • IBD-PSC patients are at higher risk for pouchitis
  • GGT of >252 U/L “was highly sensitive (99%) and had good specificity (71%) for PSC” [or ASC]
  • The authors recommend “screening all newly diagnosed patients with IBD with ALT and GGT
  • Immunosuppressive therapy is NOT effective
  • Vancomycin therapy is currently being tested (clinical trials: NCT02137668 & NCT01802073)

AIH:

  • Less frequent in IBD patients than PSC
  • Most common treatment is prednisone/azathioprine
  • 40-80% of children have cirrhosis at AIH diagnosis, but “progression to end-stage liver disease is rare and …with appropriate treatment, 80% of patients achieve remission.”

ASC:

  • ASC is an overlap syndrome between AIH and PSC
  • “It is important that children with IBD and apparent AIH are routinely investigated for evidence of biliary disease with MRCP”
  • “ASC responds to the same immunosuppressive combination therapy used for AIH”

HAV/HBV Immunization:

  • HAV vaccination is effective in patients with IBD…although the rate [seroconversion] was significantly lower” in patients receiving anti-TNF therapy (92.4% vs 99.1% in one study).
  • In those needing HBV immunization: “One strategy evaluated to improve HBV immunity in adults with IBD is an accelerated course with double vaccine doses at 0, 1, and 2 months.”

Methotrexate (MTX):

  • “The extent of histological features of hepatotoxicity secondary to long-term MTX use in IBD has been infrequently described; however, the inicdence of significant abnormal histological findings appears to be rather low.”

My take: This article is a good starting point for liver-related issues in IBD.  For concerns regarding medications, the NIH livertox website is more useful and much more comprehensive.

Related blog entries:

DILI:

PSC:

AIH:

 

 

Proof That Diet Changes Can Improve a Fatty Liver

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A recent prospective study (M Markova, O Pivovarova, et al. Gastroenterol 2017; 152: 571-85) showed that among individuals with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes that a diet high in protein (animal or plant) reduced liver fat over a 6 week period.

Among 37 participants, body fat and intrahepatic fat were detected with MRI and spectroscopy, respectively. Protein was increased to 30% of the diet. Fat was reduced to 30% and carbohydrates to 40% of diet composition. .

Key findings:

  • With a high animal protein diet, liver fat was reduced by 36%.  In the high plant protein diet group, liver fat was reduced by 48%.
  • Theses changes were unrelated to change in body weight.  However, these changes were correlated with down-regulation of lipolysis and lipogenic indices.

Some of the findings may be limited to older patients as this cohort was older than 60 years of age.  In the pediatric population, the dietary factor that has been linked most closely to NAFLD has been fructose, mainly in sugar-sweetened beverages (R Patusco et al. Top Clin Nutr 2017; 32: 27-46 -thanks to Ben Gold for this reference).

My take: This study shows improvement in liver fat with increased protein/reduced dietary fat.  While this study indicates that dietary modification is important in treating NAFLD, the optimal dietary intervention (eg. higher protein, lower sugar, lower fat) remains uncertain.

Related posts:

 

FDA Approval of HCV Medications for Children, 12-17 years

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4/7/17:  FDA Okays Two Hepatitis C Drugs for Our Pediatric Patients

An excerpt:

The US Food and Drug Administration (FDA) today granted approval for supplemental applications for sofosbuvir (Sovaldi) and ledipasvir and sofosbuvir (Harvoni) to treat hepatitis C virus (HCV) in children ages 12 to 17…

Sovaldi, combined with ribavirin, is indicated to treat pediatric patients 12 years older or weighing at least 77 pounds (35 kilograms) with genotype 2 or 3 HCV infection without cirrhosis or with mild cirrhosis.   Harvoni is indicated for the treatment of pediatric patients 12 years and older or weighing at least 77 pounds (35 kilograms) with HCV genotype 1, 4, 5 or 6 infection without cirrhosis (liver disease) or with mild cirrhosis.   The approval for the new indication was based on an open-label, multicenter clinical trial including 100 pediatric patients 12 years and older looking at the safety, pharmacokinetics, and efficacy of Harvoni to treat HCV genotype 1 infection…

health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with Harvoni or Sovaldi.

Liver Briefs -April 2017

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JA Flemming et al. Hepatology 2017; 65: 804-12.  This cohort study (2003-2015) of 47,591 adults wait-listed for liver transplantation, using the SRTR registry, showed that the era of direct-acting antivirals for hepatitis C was associated with a drop of 32% for HCV patients who were listed compared to the numbers listed during the interferon era.

AG Feldman et al. J Pediatr 2017; 182: 217-22. This retrospective study showed that elevated lactate levels (≥2.5 mmol/L) and elevated lactate to pyruvate ratio (≥25) were NOT predictive of mitochondrial diseases in pediatric patients who presented with acute liver failure.

AG Feldman et al. J Pediatr 2017; 182: 232-38. This retrospective cohort study showed a high rate of vaccine preventable illnesses (VPIs) following liver transplantation (n=2554), occurring in 1 of 6 liver transplant recipients. Most common infections was RSV; most common VPIs: rotavirus and influenza

Saint Chappelle, Paris

What Works for Itching?

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Two recent articles delve into the issue of pruritus associated with cholestasis:

  • JE Squires et al. JPGN 2017; 64: 425-430.
  • Thebaut et al. JPGN 2017; 64: 431-35.

In the first study, a single-center retrospective review of 8 patients with FIC1 disease who underwent partial exernal biliary diversion (PEBD) showed that all patients had resolution of chronic cholestasis (T bili <2 mg/dL) but 7 of 8 experience episodic cholestatic events. Pruritus improved but did not resolve.  PEBD did not obviate the need for aggressive fat-soluble vitamin supplements.

In the second study, the authors added sertraline to patients who had ongoing pruritus despite ursodeoxycholic acid and rifampin therapy.  Patients had either Alagille syndrome or PFIC (progressive familial intrahepatic cholestasis). Two patients had undergone PEBD. Sertraline was started at 1 mg/kg/day and increased as needed every two weeks to max of 4 mg/kg/day (median daily dose 2.2 mg/kg/day).  6 patients had adverse effects, including agitation (2), skin reactions (2), alopecia (1) and vomiting (1). Key finding:

  • 14 of 20 children had improved “itching score” from 8/10 to 5/10.  This correlated with improved sleep and less skin scratch marks.

 

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

Sawnee Mountain Park

March 2017 Briefs

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MC Montana, AS Evers. J Pediatr 2017; 181: 279-84. This commentary reviewed recent studies regarding anesthetic neurotoxicity. “Two recently published human studies suggest a lack of harm in otherwise-healthy children following a short duration anesthetic (approximately 1 hour)” References: Lancet 2016; 387: 239-50 & JAMA 2016; 315: 2312-20.

Related posts:

NR Santucci et al. JPGN 2017; 64: 186-93.  This systematic review selected 31 studies (out of 916 citations) and found there is no consensus concerning diagnostic criteria for biliary dyskinesia and the data supporting the concept of biliary dyskinesia in children is weak.  The uncontrolled studies were generally observational, retrospective designs with relatively small numbers.

Related posts

I Youngster et al. J Pediatr 2017; 182: 239-44.  This study examined large prescription databases (more than 74 million person years) and identified wide discrepancy in antibiotic use among the six different countries.  For example, among children less than 2 years of age, South Korea had the highest rate of antimicrobial use, with 3.41 prescribed courses per child-year; in contrast, the rates were 1.4 in Italy, 1.5 in Spain, 1.1 in the U.S., 1.0 in Germany, and 0.5 in Norway.

A Srivastavai et al. JPGN 2017; 64: 194-9. In this retrospective study with 262 children with liver disease-related ascites, the authors found spontaneous bacterial peritonitis (or culture-negattive neurocytic ascites) in 28.6%. Half of these patients were asymptomatic.  SBP/CNNA was defined by having a polymorphonuclear leukocyte count of >250 cells/mm3.  There was a 24% one-year mortality rate for those who had SBP/CNNA.

MR Narkewicz et al. JPGN 2017; 64: 210-7. Using data from the pediatric acute liver failure group, the researchers identified a high rate of autoantibodies (28%) among 986 pediatric subjects with acute liver failure. The presence of autoantibodies was not significantly associate with 21-day outcomes and steroid treatment was not associated with survival; in fact, those without a known diagnosis of autoimmune hepatitis, had a higher risk of death with steroid therapy. In the setting of acute liver failure, autoantibody positivity does not obviate the need for a complete diagnostic workup.

A Lauterio et al. Liver Transplantation 2017; 23: 184-93.  Italian review of living donor safety found that major complications occurred in 12.6% (31 or 246)  but there were no mortalities. 5 (2%) required reoperation.

 

from Twitter's 'This Week in Church Signs' feed

from Twitter’s ‘This Week in Church Signs’ feed

Rising Rates of Pediatric Fatty Liver

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The alarming rates of pediatric nonalcoholic fatty liver disease are summarized in a recent Lancet Blog (Thanks to John Pohl for this link).  Seven million children in U.S. have fatty liver disease.

Link: An alarming trend in fatty livers (in children)

An excerpt:

The rate of NAFLD among US children has tripled over the last twenty to thirty years, rising from 3-4 percent to 10-11 percent, according to Dr. Naim Alkhouri, Director of the Metabolic Liver Center at the Texas Liver Institute in San Antonio…

Lifestyle changes, such as better nutrition and increased exercise, are currently the best-known way of mitigating and possibly reversing its effects…

Some 35-50 percent of obese children have NAFLD, and 20 percent of children with NAFLD have the advanced form of NASH. Also, 10-15 percent of children with NAFLD are in a predicament that could be described as “pre-cirrhosis.”

“Though most cases of juvenile NAFLD are caused by excess weight and associated insulin resistance, “up to 7% of non-overweight or obese children may have NAFLD,” according to a new study that Alkhouri and others will present at the upcoming International Liver Congress, held in Amsterdam this April.

Related blog posts:

Chattahoochee near Azalea Drive

Chattahoochee near Azalea Drive