Category Archives: Pediatric Gastroenterology Liver Disease

Good News Story: The Remarkable Hepatitis B Vaccine Story

Posted on by

W-Q He, GN Guo, C Li. Hepatology 2022; 75: 1566-1578. The impact of hepatitis B vaccination in the United States, 1999-2018

In the past 30 years, the hepatitis B vaccine has been included in infant immunization schedules in the U.S. The authors studied a large, comprehensive, and nationally representative data set (NHANES data from 1999-2018) to assess its efficacy.

Key findings:

  • HBV vaccination was associated with reduced risk of all-cause mortality (HR, 0.78; 95% CI, 0.68–0.90) and cancer-related mortality (HR, 0.76; 95% CI, 0.58–1.00) 
  • The highest vaccination uptake was found among those born after 1991, at 86.5%.
  • Vaccinated participants had higher prevalence of vaccine-induced immunity than the unvaccinated (47.2% vs. 7.4%). Among those born after 1991, vaccine efficacy (VE) was found at 58% (95% CI, 18%–79%) overall and 85% for those aged ≥20 years (mean age, 22), whereas no effect was found among those born prior to 1990

Context for these findings is noted in the associated editorial (pgs 1365-1367):

HBV remains one of the most deadly viruses worldwide with nearly 1 million deaths yearly and nearly 300 million people chronically-infected. The vast majority of unvaccinated children less than 1 year of age become chronically-infected. In the U.S., 98% of children acquired HBV through vertical transmission “including 26% of pediatric cases who were born in the USA or Canada”

My take: This study shows that HBV vaccine maintains strong protection for 20 years and protects against cancer and death.

Related blog posts:

Los Poblanos Ranch, Alburquerque

Efficacy of Sebelipase Alfa for Lysosomal Acid Lipase Deficiency

Posted on by

BK Burton et al. JPGN 2022; 74: 757-764. Open Access: Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency

This was open-label study of enzyme replacement therapy (ERT) in 31 children and adults with lysosomal acid lipase deficiency (LALD). Sebelipase Alfa, a recombinant human lysosomal acid lipase, was FDA approved in 2015 for LALD.

Key findings:

  • Liver biopsies showed mostly improved or stable histopathology at 48 and 96 weeks versus baseline. In addition, there was modest improvement in transaminases; median ALT and AST levels changed by −42.0 and −22.0 U/L, respectively.
  • Median low-density lipoprotein cholesterol levels decreased by 52.6 mg/dL, and median high-density lipoprotein cholesterol increased by 9.8 mg/dL. Though, 55% of the study population had concomitant lipid-modifying therapy
  • Two patients tested positive for nonneutralizing, anti-drug antibodies

In the associated commentary (pgs 726-727), the authors state this study showed that “in contrast to infantile disease, ERT is not universally beneficial in individuals with attenuated disease…[and] it is impossible to predict response to ERT.” Testing for LALD is recommended for infants with hepatomegaly, poor growth, diarrhea or adrenal insufficiency. In older groups, LALD needs to be considered in those with hepatomegaly, steatosis, and dyslipidemia.

My take: There are still many questions regarding ERT’s long-term benefit in individuals with LALD, especially those with mild disease.

Related blog posts:

From NASPGHAN Newsletter

Type 2 Diabetes in Children with Nonalcoholic Fatty Liver Disease

Posted on by

JB Schwimmer et al. Clin Gastroenterol Hepatol 2022; DOI:https://doi.org/10.1016/j.cgh.2022.05.028. Pre-proof full text PDF:Incidence of Type 2 Diabetes in Children with Nonalcoholic Fatty Liver Disease

Methods: Children with NAFLD (n=892) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. These children had a mean age of 12.8 years followed for a mean of 3.8 years 

Key findings:

  • At baseline, 63 (of 892) children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8 %.
  • Incident T2D was significantly higher in females versus males (HR 1.8 [1.0-2.8]), associated with BMI z-score (HR 1.8), and more severe liver histology including steatosis grade (HR 1.3), and fibrosis stage (HR 1.3).

My take: Children/adolescents with NAFLD need to be monitored for the development of T2D.

Related blog posts:

Thanks to David for picture of Portland Head Lighthouse

Wow, Your Liver Looks So Young!

Posted on by

I’ve had the good fortune to work with the same nurse, Bernadette, for 25 years. While I have joked with some patients, that in a few more years she will figure it all out, in fact, she has been terrific from day one. A few years ago, Bernadette enthusiastically told me that her physician had told her that she had the colon of a teenager; this sounds like a good thing.

I was thinking about this comment about younger body parts after reading a recent article from The Washington Post (6/6/22): Your liver is younger than you think

Key points/excerpts:

  • “Research in the journal Cell Systems reveals that humans’ livers are forever young, clocking in at less than three years old despite their hosts’ biological age…”
  • “Researchers studied the livers of 33 adults who were between ages 20 and 84 when they died…When the scientists dated the cells, they found an average age of about three years regardless of the age of the person who generated the cells. The hepatocytes “show continuous and lifelong turnover, allowing the liver to remain a young organ,” they write.”
  • “Ninety-five percent of the cells with two complete sets of chromosomes turned over within a year, but up to 12 percent of a cell subtype that have more than one pair of chromosomes can survive up to a decade.”
  • “Our bodies produce about 700 million hepatocytes each day — not bad for a three-pound organ.”

My take: The liver is amazing and can stay young even when in older bodies.

Related blog post: Why the Liver is the King of Internal Organs

Liver Shorts: Malnutrition in Biliary Atresia, Cholestasis with ECMO, Impaired Cognition After Pediatric Liver Transplantation

Posted on by

JM Boster et al. Liver Transplantation 2022; 28: 483-492. Malnutrition in Biliary Atresia: Assessment, Management, and Outcomes Good review article. Malnutrition and sarcopenia negatively impact pretransplant, peritransplant, and posttransplant outcomes and survival in children with BA.

E Alexander et al. JPGN 2022; 74: 333-337. Clinical Implications for Children Developing Direct Hyperbilirubinemia on Extracorporeal Membrane Oxygenation Key findings: 36/106 (34%) children developed direct hyperbilirubinemia (DHB) on ECMO. Illness acuity scores were significantly higher in the DHB group on ECMO day 2 (P = 0.046) and day 7 (P = 0.01). Mortality rate was higher in the DHB group 72%, versus 29% in the control group (P < 0.001).

A Ostensen et al. J Pediatr 2022; 243: 135-141. Open Access: Impaired Neurocognitive Performance in Children after Liver Transplantation In this study with 65 participants, key findings:

  • Compared with the patients who underwent transplantation a age >1 year (n = 35), those who did so at age <1 year (n = 30) had a lower FSIQ (87.1 ± 12.6 vs 96.6 ± 13.8; P = .005) and lower verbal comprehension index (87.3 ± 13.8 vs 95.4 ± 13.0; P = .020).
  • Transfusion of >80 mL/kg (P = .004; adjusted for age at transplantation: P = .046) was also associated with detrimental effects on FSIQ.
  • No difference in IQ between tests was found in those patients tested more than once, indicating no significant improvement with more time after transplantation (first testing was at median of 4.1 years after transplantation and the second testing was at a median age of 6.7 years after transplantation)
  • “Our findings indicate that transplantation at early age has a pronounced effect on later neurocognitive impairment, and that this effect is separate from and more pronounced than the effect of cholestasis before transplantation.”

Related blog posts:

Onion Headline:

Genetic Diseases and Newborn Unconjugated Hyperbilirubinemia

Posted on by

H Mel et al. J Pediatr 2022; 243: 53-60. Clinical and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project

Methods: The researchers used targeted panel sequencing data on 2742 genes including known unconjugated hyperbilirubinemia genes in 1412 neonates (in China). Exclusion criteria included gestational age <35 weeks and congenital malformations. 37% had severe unconjugated hyperbilirubinemia (reaching threshold recommended for exchange transfusion)

Findings:

  • 45 (3%) of the cohort had genetic findings related to their unconjugated hyperbilirubinemia. 26 had variants associated with G6PD deficiency and eight had variants in UGT1A1 (which can cause Gilbert syndrome or Crigler-Najjar syndrome)
  • 11 of 45 of genetic findings were due to more obscure causes including to RBC membrane defects, n=5 (ANK1, SPTB) and due to metabolic/biochemical disorders (GCDH, MMACHC, MUT, DUOX2, DUOXA2, MOCS1)
  • Known clinical causes of hyperbilirubinemia were identified for 68% of patients. The most common clinical cause of unconjugated hyperbilirubinemia group was infection (15%). Other clinical causes included breastfeeding (n=154, 11%), extravascular hemorrhage (147, 10%), hemolytic disease (104, 7%) and inadequate feeding (82, 6%)

My take: About 3% of infants in this cohort had underlying genetic causes contributing to their jaundice; three-fourths of those with a genetic condition had either a variant of G6PD or UGT1A1

Related blog posts:

Valley of Fires, New Mexico. The darker areas are lava.

Sugary Beverage and Liver Stiffness in Healthy Adults

Posted on by

CW Leung, EB Tapper. Clin Gastroenterol Hepatol 2022; 20; 959-961. Sugar-sweetened Beverages Are Associated With Increased Liver Stiffness and Steatosis Among Apparently Healthy Adults in the United States

In this representative sample (2706 adults, median 37.9 years) from 2017-2018 NHANES, subjects without any known chronic disease had tow 24-hr dietary recalls collected and had liver stiffness measurements (LSM) and controlled attenuation parameters (CAP); LSM <7 kPa (using vibration-controlled transient elastography) was considered low risk for advanced fibrosis and CAP >248 dB/m were at risk for heaptosteatosis. Key findings:

  • 11% (n=305) had LSM >7.0 kPa and 46% (n=1254) had CAP >248 dB/m
  • Sugar-sweetened beverage (SSB) >2/day was associated with greater LSM (OR 2.30)
  • In mutlivariate analysis, consuming >1-2 sugar-sweetened servings per day was associated with elevated CAP (OR 1.51 compared to adults with SSB consumption
  • Limitations: this cross-sectional study cannot prove causality

My take: Even in healthy adults, SSB consumption is associated with detrimental changes in the liver.

Related blog posts:

Lessons Learned from Children In the Hepatitis B Virus Research Network

Posted on by

SJ Schwarzenberg et al. JPGN 2022. 74: 431-433. Lessons Learned from Children Enrolled into the Hepatitis B Virus Research Network Multi-Center Prospective Study

This NIDDK-funded Hepatitis B Research Network (HBRN) was established in 2009 and enrolled 362 patients. 97% of participants were born in countries where HBV is endemic or in North America to mothers born from these countries.

Key points:

  • Due to revised criteria for ALT values, most pediatric patients have elevated ALT and do not meet the definition of immune-tolerant
  • Spontaneous flares (ALT >400 in males and >350 in females) in untreated children…did not lead to hepatic decompensation
  • Hepatocellular carcinoma was not identified in this cohort, though HBRN centers reported historical experiences. Only one patient developed cirrhosis over 4 years of followup.

Clinical Recommendations from Authors:

  • Screen for HBV in children with unexplained serum aminotransferases regardless of immunization history
  • Screen for HBV in children with normal aminotransferases if they or their parents are from an area where HBV is endemic or other risk factors
  • In those with HBV, monitor aminotransferases and HBV levels every 6 months
  • Obtain genotype in children with HBV
  • Consider treatment if ALT >2 x ULN over 3-6 mo. Treatment should follow AASLD guideline
  • Recommend AGAINST treatment at the start of a flare
  • Recommend counseling to promote healthy weight and avoidance of at-risk alcohol use

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

How Much Testing Is Needed In Children with Suspected Fatty Liver?

Posted on by

F Al-Harthy et al. JPGN Reports 2022; Volume 3 – Issue 2 – p e181. doi: 10.1097/PG9.0000000000000181. Open Access: Evaluation of Hepatitis in Pediatric Patients With Presumed Nonalcoholic Fatty Liver Disease

In this single-center retrospective study (2017–2020), the authors reviewed the extent of testing and yield in children with suspected NAFLD. Criteria:

  • BMI >85th percentile
  • Persistently (>3 months) elevated ALT more than twice the ULN for age
  • Radiographic (ultrasound, computed tomography, and MRI) features of hepatic steatosis.

Key findings:

  • Eleven (11.6%) patients were ultimately diagnosed with a condition resulting from their abnormal bloodwork: infectious hepatitis (3, 9.8%), thyroid disease (2, 3.4%), celiac disease (4, 7.7%), AIH (1, 1.7%; diagnosis based on liver biopsy), and A1AT deficiency (1, 2.0%). It is likely that the yield would have been higher if all patients had more extensive testing
  • Only 9.5% of patients had comprehensive, additional testing performed per the 2017 North American Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines: infectious hepatitis serologies (Hepatitis A virus IgM, Hepatitis B surface antigen, anti–Hepatitis C virus), thyroid studies (thyroid-stimulating hormone [TSH]), ceruloplasmin, A1AT, liver autoantibodies (antinuclear antibody; anti-smooth muscle antibody; liver kidney microsome type 1 antibody), tissue transglutaminase IgA (TTG-IgA), total IgA, total IgG, and LAL blood spot
  • The costs of performing the recommended testing was estimated as $397.30 Canadian dollars

My take: In those with persistently elevated liver enzymes, additional blood tests are important to evaluate for chronic liver diseases, even in those suspected of NAFLD.

Related blog posts on fatty liver disease:

Shem Creek, SC

Liver Transplant Outcomes in Children: Two Studies

Posted on by

Jean de Ville de Goyet et al. Hepatology 2022; 75: 634-645. European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children

This is an amazing study — “50-year period (1968–2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children).”

Key findings:

  • Overall, the 5-year graft survival rate has improved from 65% in group A (before 2000) to 75% in group B (2000-2009) (p < 0.0001) and to 79% in group C (since 2010) (B versus C, p < 0.0001).
  • Graft half-life was 31 years, overall; it was 41 years for children who survived the first year after transplant.
  •  The use of living donors steadily increased from A to C (A, n = 296 [7%]; B, n = 1131 [23%]; and C, n = 1985 [39%]; p = 0.0001)

My take: Liver transplantation provides a durable cure for most infants and children with severe liver disease.

A Shingina et al. Liver Transplantation 2022; 28: 437-453. Long-term Outcomes of Pediatric Living Versus Deceased Donor Liver Transplantation Recipients: A Systematic Review and Meta-analysis

Associated editorial: EM Dugan, AD Griesemer. Pediatric Living Donor Liver Transplantation: Optimizing Outcomes for Recipients, Donors, and the Waiting List

A total of 24 studies with 3677 patients who underwent living donor liver transplantation (LDLT) and 9098 patients who underwent deceased donor liver transplantation (DDLT) were included for analysis. Key findings:

Overall, this meta-analysis shows improved patient and graft survival at 1, 3, 5, and 10 years with LDLT compared to DDLT:

  • Patient survival: LDLT vs DDLT: 1-year (odds ratio [OR], 0.68), 3-year (OR, 0.73), 5-year (OR, 0.71), and 10-year (OR, 0.42)
  • Graft survival — LDLT vs DDLT: 1-year (OR, 0.50), 3-year (OR, 0.55), 5-year (OR, 0.5; 95), and 10-year (OR, 0.26)

While LDLT is often technically more challenging, it provides timely access (reducing wait-time deaths/deterioration) to a high-quality organ with minimal preservation time. In this cohort, LDLT patients had higher MELD and PELD scores at transplantation compared to the DDLT.

My take: Increasing use of LDLT, at centers with appropriate expertise, will lead to better outcomes in children with severe liver disease.

Related blog posts:

Chattahoochee River in Sandy Springs, Ga