Category Archives: Pediatric Gastroenterology Liver Disease

Liver Briefs -September 2019

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P Rosenthal et al. Hepatology 2019; 69: 2326-37.  This study examined the efficacy and safety of combined entecavir and Peginterferon for immune-tolerant chronic hepatitis B-infected children (n=60). 48 weeks after completing treatment (week 96), 2 children (3%) achieved the primary outcome of undetectable HBeAg with HBV DNA levels <1000 IU/mL.  These two children were also HBsAg negative/anti-HBs positive. In the other children (55 completed study), the ALT and HBV DNA levels were similar to baseline.  37 children experienced adverse events.  My take: Entecavir/peginterferon is not very effective in immune-tolerant children infected with chronic HBV.

DL Thomas. NEJM 2019; 380: 2041-50. This article reviews the pathway to the global elimination of chronic hepatitis.  Currently, it is estimated that hepatitis C virus (HCV) and hepatitis B virus (HBV) kill more than 1 million persons each year. “In fact, by 2040, deaths from chronic hepatitis are projected to exceed the combined mortality associated with HIV infection, tuberculosis, and malaria.”

JR Dillman et al. J Pediatr 2019; 212: 60-5. This study with 41 patients and 13 patients with biliary atresia prospectively assessed ultrasound shear wave elastography (SWE). The authors found that SWE with a cut-off value of >1.84 m/s had 92% sensitivity and 79% specificity.  Also, in their cohort, GGT >320 had a sensitivity of 100% and specificity of 78%.

Z Younossi et al. Hepatology 2019; 69: 2672-82.  This review provides a global perspective of NAFLD.  25% of the world’s population is currently thought to have NAFLD with highest prevalence in South America at 30.45% and lowest in Africa at 13.5%. This article usggest North America to have 24.1% prevalence rate.

Briefly Noted: Alpha-Fetoprotein Norms for Beckwith-Wiedeman Spectrum

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Alpha-fetoprotein (AFP) levels are increased in >95% of patients with hepatoblastoma.  These levels have to be interpreted carefully in infants as these levels typically are elevated in the first 6-12 months of life.

For patients with Beckwith-Wiedeman Spectrum (BWS), the relative risk of hepatoblastoma has been estimated to be 2280 times greater than the general population.  In addition, in patients with BWS, AFP levels are known to be elevated compared to the general population in the absence of hepatoblastoma as well.

A recent study (KA Duffy et al. J Pediatr 2019; 212: 195-200) obtained 1372 AFP levels from 147 patients to establish normative values.

Table 2 -will be a useful reference. The authors found that AFP values were significantly higher in premature infants with BWS compared to full term and gradually approached normal levels around 12 months of life.

Some example AFP (95% CI) values from the entire cohort:

  • 1 week 5364 (3554-8095)
  • 4 weeks 3134 (2136-4597)
  • 12 weeks 849 (613-1176)
  • 6 months 134 (102-177)
  • 12 months 13.8 (11.1-17.3)

My take: This article will be very useful when monitoring for the risk of hepatoblastoma in patients with BWS

 

 

SMOFlipid vs. Intralipid for Intestinal Failure Patients

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A recent study (C Belza et al. JPEN 2019; https://doi.org/10.1002/jpen.1692) showed that SMOFlipid reduced the frequency of cholestasis in intestinal failure patients. Thanks to Kipp Ellsworth for reference.

An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure–Associated Liver Disease in Infants With Intestinal Failure. From Abstract:

Methods

This was a retrospective cohort study of infants with IF with a minimum follow‐up of 12 months in 2008–2016. Patients were stratified into 2 groups: group 1 received SMOFlipid; group 2 was a historical cohort who received Intralipid. The primary outcome was liver function evaluated using conjugated bilirubin (CB) levels…

Results

Thirty‐seven patients were evaluated (17 = SMOFlipid, 20 = Intralipid). SMOFlipid patients were less likely to reach CB of 34 (24% vs 55%, P = 0.05), 50 µmol/L (11.8% vs 45%; P = 0.028), and did not require Omegaven (0% vs 30%; P = 0.014). CB level at 3 months after initiation of parenteral nutrition (PN) was lower in patients receiving SMOFlipid (0 vs 36 µmol/L; P = 0.01). Weight z‐scores were improved for patients receiving SMOFlipid at 3 months (−0.932 vs −2.092; P = 0.028) and 6 months (−0.633 vs −1.614; P = 0.018).

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Crater Lake, OR

Liver Shorts August 2019

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JB Talcott et al. JPGN 2019; 69: 145-51.  This small study showed an association with prolonged cholestastic liver disease in children and poorest cognitive outcomes despite successful transplantation.  There were 28 participating children in this study, only 12 with chronic liver disease. Acute liver disease was not associated with deficits in cognitive function.  This study “reinforces the need for timely intervention.”

AA Butt et al. Gastroenterol 2019; 156: 987-96.  This study which used a Veterans database for chronic hepatitis C (HCV) infection (n=242,680) found that treatment with direct-acting antiviral therapy (hazard ratio 0.57) was associated with a significant decrease in risk of cardiovascular disease events.

F DiPaola et al JPGN 2019; 69: 152-59.  This study from the drug induced liver injury (DILI) network (2004-2017) with just 57 cases found that antimicrobials (51%) and antiepileptics (21%) were the leading causes of DILI in children. Related blog: Liver toxicity –Where to Look Online

P Huelin et al. Hepatology 2019; 70: 319-33. This study with 320 consecutive cases of acute kidney injury (AKI) in patients hospitalized for cirrhosis found that urinary neutrophil gelatinase-associated lipocalin (NGAL) (best at day 3) helped differentiate acute tubular necrosis from other types of AKI.

Risk Factors for Progressive, Fibrotic Fatty Liver Disease

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Briefly noted: A recent study (A Mosca et al. J Pediatr 2019; 211: 72-7) examined 182 obese/overweight children with nonalcoholic fatty liver disease (NAFLD). 137 (75.3%) had liver fibrosis. 39 had fibrosis level ≥2 (21.4%)

Risk factors for liver fibrosis:

  • Not being breastfed OR 3.1
  • Parenteral obesity OR 2.9
  • PNPLA3 (palatin like phospholipase domain-containing 3) GG (1148M) variant OR 2.1
  • Fructose consumption (OR 1.6 per 1 g/day increase)
  • Vitamin D deficiency (25-OH <20 mg/dL) OR 1.24
  • A high socioeconomic status was inversely associated with fibrosis OR 0.3

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How To Diagnose Biliary Atresia in 48 hrs

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From Cincinnati Children’s e-Newsletter

An excerpt:

New Test Expedites the Diagnosis of Biliary Atresia

A groundbreaking test developed at Cincinnati Children’s can expedite a diagnosis of biliary atresia (BA), helping physicians decide quickly whether to perform a liver biopsy followed by an operative cholangiogram, the definitive test for BA. The test quantifies the concentration of MMP-7 (matrix metalloproteinase-7), a serum protein that researchers at Cincinnati Children’s discovered in 2017 is a biomarker of BA.

Physicians can order the MMP-7 assay by submitting a requisition form. Test results are available within 48 hours, and a pediatric hepatologist is always available for consultation regarding the interpretation of test results.

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Liver Briefs -July 2019

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NH Ebel et al. JPGN 2019; 68: 788-92.  Hepatic venous pressure gradient (HVPG) did not correlate with the risk of complications from portal hypertension in this pediatric cohort (n=41); this is in contrast to studies in adults showing the utility of HVPG measurements.

AG Singal et al. Gastroenterol 2019; 156: 2149-57. AGA Practice Update on Direct-Acting Antivirals for Hepatitis C and Hepatocellular Carcinoma. There are 12 best practice advice –here are the first three:

  • BEST PRACTICE ADVICE 1: DAA treatment is associated with a reduction in the risk of incident HCC. The relative risk reduction is similar in patients with and without cirrhosis.
  • BEST PRACTICE ADVICE 2: Patients with advanced liver fibrosis (F3) or cirrhosis should receive surveillance imaging before initiating DAA treatment.
  • BEST PRACTICE ADVICE 3: Patients with advanced liver fibrosis (F3) or cirrhosis at the time of DAA treatment represent the highest-risk group for HCC after DAA-induced sustained virologic response. These patients should stay in HCC surveillance

N Hamdane et al. Gastroenterol 2019; 156: 2313-29. This study found that chronic HCV infection induced specific genome-wide-changes in H3K27ac which correlated with expression of mRNAs and proteins.  These epigenetic changes persisted after an SVR to DAAs or interferon-based therapies. These changes could explain some of the reason why HCC remains a risk after successful treatment with DAAs.

DT Dieterich et al. Gastroenteroloy & Hepatology 2019; 15S: 3-11 Link: “A simplified algorithm for the management of Hepatitis C Infection”  An excerpt:

“The algorithm begins with universal HCV screening and diagnosis by testing for HCV antibody with reflex to polymerase chain reaction to detect HCV RNA. The pretreatment evaluation uses platelet-based stratification to initially assess fibrosis, and the pan-genotypic regimens glecaprevir/pibrentasvir or sofosbuvir/velpatasvir are recommended for treatment. Unless clinically indicated, on-treatment monitoring is optional. Confirmation of cure (undetectable HCV RNA 12 weeks posttreatment) is followed by harm-reduction measures, as well as surveillance for hepatocellular carcinoma every 6 months in patients with advanced fibrosis/cirrhosis.”  My take: This algorithm is much simpler than the expanded recommendations from HCVguidelines.org website, though these agents, to my knowledge, do not yet have a pediatric indication.

 

Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis

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A large retrospective study (M Deneau, M Perito, A Ricciuto, N Gupta et al. J Pediatr 2019; 209: 92-6) examined the outcomes/response of ursodeoxycholic acid (UDCA) for pediatric primary sclerosing cholangitis (PSC).

Background:

  • “Within 10 years of diagnosis, 30% of children with PSC will require liver transplantation and 50% of children will develop complications, including biliary strictures and hypertension.”
  • Because UDCA has not been shown to improve survival (& may worsen outcomes), it is not recommended in adults by the AASLD.
  • In pediatrics, UDCA remains the most common treatment, used in more that 80% on long-term treatment

Study population/methods:

  • 263 patients at 46 centers
  • Median age 12.1 years
  • UDCA median dose: 15 mg/kg/day

Key findings:

  • Normalization of GGT (<50 IU/L) occurred in 46% of patients in the first year after diagnosis
  • Patients with normalization was less likely among patients with Crohn’s disease and those with laboratory profiles indicative of more advanced hepatobiliary fibrosis (eg. lower platelet count, lower albumin, hyperbilirubinemia)
  • The 5-year survival with native liver was 99% in those who achieved normalization vs 77% in those who did not
  • Even in those without normalization, improvement in GGT was associated with better outcomes. “Those who had a reduction in GGT of >75% had nearly the same long-term survival as those with GGT<50 IU/L at 1 year.”
  • It has previously been shown that nearly “one-third of children who are UDCA-naive have spontaneous GGT normalization by 1 year.”  Thus, the number to treat with UDCA to have one additional case of GGT normalization is four.
  • In a previous study, one-third of patients with GGT normalization on UDCA therapy for 1 year, maintained GGT <29 after withdrawal of UDCA for 12 weeks.

The authors note that “patients who do not achieve normalization could reasonably stop UDCA as they are likely not receiving clinical benefit.”

My take: This study shows that patients who have improvement/normalization of GGT with UDCA therapy have improved outcomes.  The retrospective design of the study limits conclusions about whether UDCA therapy actually improves long-term outcomes, particularly since UDCA at higher doses has been associated with detrimental affects in adults with PSC.

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Pablo Picasso, Le Compotier (Fruit Bowl) at Sofia Reina
https://www.museoreinasofia.es/en/collection/artwork/compotier-fruit-bowl

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.

Liver Briefs -June 2019 part 2

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E Cowell et al. JPGN 2019; 68: 695-99. This study reviewed 61 cases of pediatric hepatocellular carcinoma to determine predisposing conditions  (in Houston TX).  The majority did NOT have recognizable predisposing conditions.  25 of 61 (41%) had a predisposing condition including cryptogenic cirrhosis/steatosis (9), genetic (7), biliary pathology (4), viral hepatitis (1), and other (4).  Those without a recognizable predisposing condition were diagnosed later and with more advanced disease/decreased survival.

VA McLin et al. JPGN 2019; 68: 615-22. Useful review on congenital portosystemic shunts.

DE Kaplan et al. Gastroenterol 2019; 156: 1693-1706. This large study form the VA with more than 70,000 patients examined the relationship between statin exposure and survival in patients with cirrhosis.  “Each cumulative year of statin exposure was associated with an independent 8-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.”

AG Singal et al. Gastroenterol 2019; 156: 1683-1692. Direct-acting antiviral therapy was not associated with recurrent hepatocellular carcinoma (HCC) in a multicenter cohort study with 793 patients with HCV-associated HCC. Thus, DAAs appear safe in patients who have achieved a complete response to HCC Rx

Liver Briefs -June 2019

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YH Yeo et al. Hepatology 2019; 69: 1385-97.  The prevalence of high risk individuals in the U.S. who are susceptible (not immune) to hepatitis B has decreased from 83% to 69% from 2003 to 2014.  That still leaves 64 million who would benefit from HBV vaccination.

M Sharma et al. Hepatology 2019; 69: 1657-75. This meta-analysis compared therapies for primary prevention of esophageal varices and concluded that nonselective beta-blocker (NSBB) monotherapy may decrease all-cause mortality and carried a lower risk of serious complications than variceal band ligation (VBL). However, the commentary (1382-84 by L Laine) reaches a different conclusion. “Current recommendations for primary prevention with VBL or NSBB or carvediolo still appear to be acceptable…using a shared decision-making approach” to weigh issue such as daily medication or periodic endoscopy.

J Nguyen et al. J Pediatr 2019; 207: 90-6. This study modeled the cost-effectiveness of early treatment with direct-acting antiviral therapy in adolescents with hepatitis C infection.  With pangenotypic agenst, the cost would be $10000 to $21000 per QALY gained.

S Trinh et al. Clin Gastroenterol Hepatol 2019; 17: 948-56. This retrospective hepatitis B study examined the changes in renal function between 239 tenofovir disoproxil fumarte (TDF) treated patients and 171 entecavir treated patients.  Key finding: TDF was not associated with higher risk of worsening renal function in this cohort with a mean followup of 43-46 months in patients with baseline normal renal function.  In patients with renal impairment, deterioration of renal function was noted in TDF-treated patients.  Thus, TDF should be avoided in patients with impaired renal function.

 

Rhododendrom in Sandy Springs

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