This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).
N Ravanbakhsh et al J Pediatr Gastroenterol Nutr. 2024;79:1192–1198. Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease
In this retrospective review with 77 patients who had liver biopsy-proven MASLD (2017-2023), the authors examined how well magnetic resonance elastoraphy (MRE) and transient elastography (TE) identified fibrosis.
Key findings:
Conclusion of authors: “MRE and TE did not accurately predict high-grade fibrosis on liver biopsy. Between the two noninvasive imaging modalities, the correlation of identifying high-grade fibrosis was not statistically different.”
My take: Even MRE is not very accurate at identifying fibrosis. Given the huge numbers of individuals (pediatric and adult) with MASLD, the lack of reliable non-invasive markers is a problematic. As effective treatments become available, being able to determine if they are working is essential.
Related blog posts:
AK Jain et al. JPGN 2024; 79:943–953. Open access: Environmental toxicants modulate disease severity in pediatric metabolic dysfunction-associated steatohepatitis
This study correlated environmental toxins and steatotic liver disease. Four hundred and thirty-five children distributed across MASH (n = 293) and MASLD (n = 142), with 304 (69.9%) males. Toxins analyzed: PFAS chemicals included perfluorohexane-1-sulphonic acid (PFHXS), perfluorononanoic acid, perfluorooctanoic acid, and perfluorooctanesulfonic acid and PBDE included 2,2′,4,4′-tetrabromodiphenyl ether (BDE47), 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99), and 2,2′,4,4′,6-pentabromodiphenyl ether (BDE100).
Key findings:
My take: Not surprisingly, our environmental exposures influence the severity of steatotic liver disease. There is widespread exposure to pollutants and the full toll on our health is not clear.
Related blog posts:
N Ravanbakhsh et al. JGPN 2024; https://doi.org/10.1002/jpn3.12368. Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease
Key findings:
The authors note that previous adults studies suggest that MRE is more accurate in the identification of liver fibrosis than TE (MRE detected ≥ F1 fibrosis with an AUROC of 0.82, while TE detected fibrosis with an AUROC of 0.67).20
My take: Trying to identify accurate non-invasive testing is crucial to help identify patients most in need of treatment and for limiting costs.
Related blog posts:
PS Rolfes et al. J Pediatr 2024; 272: 114080. Establishing Neonate-Specific Prognostic Markers in Acute Liver Failure: Admission Alpha Fetoprotein and Novel Neonatal Acute Liver Failure Scores Predict Patient Outcomes
Methods: A single-center, retrospective chart review (n=51) was conducted on neonates ≤ 30 days of life between 2005 and 2022 with ALF (international normalized ratio ≥ 2 or prothrombin time ≥ 20s and liver dysfunction). This excluded infants who responded to a single dose Vit K injection or fresh frozen plasma. The age at presentation was 4.7 in survival with native liver (SNL) group and 6.9 in the non-SNL group.
Key findings:
In the discussion, the authors note that AFP may have high prognostic value at time of admission (similar to neonatal ALF model), especially in Non-GALD patients. AFP Is a “biomarker for hepatic regeneration….Similar to our findings, several adult studies have shown that elevated AFP levels are associated with favorable outcomes in non-oncologic liver diseases…Specifically, it has been shown that in ALF, rising levels of AFP during hospitalization are associated with favorable outcomes.”
My take: Both the AFP and the neonatal ALF score had similar prognostic value for SNL.
Related blog posts:
A Lundberg Bave et al. Hepatology 2024; 80: 527-535. Autoimmune diseases in primary sclerosing cholangitis and their first-degree relatives
Methods: Using National Swedish registries, the authors evaluated a matched cohort study, 1378 individuals with PSC and 13,549 general population comparators and their first-degree relatives.
Key findings:
My take: Keep an eye out for other autoimmune diseases in patients (& their 1st-degree relatives) with PSC.
Related blog posts:
Briefly noted: BB Lai et al. Hepatology 2024; 80: 511-526. Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency–related cholestasis Key finding: “Patients with the TJP2-C genotype carrying PPTMs [predicted protein-truncating mutation] in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.”
A recent case reminded me of the quote by Helena Ravenclaw in Harry Potter: “”If you have to ask, you’ll never know. If you know, you need only ask.”
One of my colleagues recently diagnosed a teenage boy with ulcerative colitis. His past medical history was notable for ADHD. At the time of his evaluation, he was noted to have an elevated AST.
Labs:
The concern at the time was whether his elevated AST should preclude using his ADHD medicine and whether there was an underlying liver disease. Based on the pattern of liver enzyme abnormalities, it was suspected that the patient had macro AST. A blood test was sent to the Mayo clinic and confirmed this diagnosis:
“”The sample was investigated for the presence of macro AST by polyethylene glycol (PEG) precipitation. Serum AST activity = 316 U/L. The AST result post-PEG precipitation = 22 U/L. The results obtained are positive for the presence of macro AST (93% of activity precipitated with PEG). Based on validation studies performed at the Mayo Clinic, a cut-off of >80% AST activity precipitated by PEG indicates the presence of macro AST.” This test is rarely ordered at the Mayo Clinic and is ordered as a miscellaneous test; it is not on the Mayo Clinic’s regular test menu.
Internet description of macro AST: Macro-aspartate aminotransferase (macro AST) is a rare, benign condition that causes a persistent elevation of aspartate aminotransferase (AST) levels in the blood. It’s caused by the binding of AST to immunoglobulins, which results in a high molecular weight macroenzyme that’s excreted from the serum more slowly than normal.
My take: Macro AST diagnosis is useful –it helps eliminate the concern for other conditions. Since it is quite uncommon, it is easier to think of this problem once you have seen it before.
Related blog posts:
N Ma et al. JPGN 2024; 79:229–237. Fibrosis and steatotic liver disease in US adolescents according to the new nomenclature
Methods: Among 1410 adolescents (12–19 years) in NHANES (2017-March, 2020), the controlled attenuation parameter (CAP) of transient elastography (TE) was used to define steatosis and fibrosis (TE ≥ 7.4 kPa). Obesity and alanine aminotransferase (ALT) ≥ 80 U/L were used to identify adolescents qualifying for hepatology referral according to practice guidelines.
Key findings:
My take: This study identifies potential problems with current thresholds for which patients need to be seen by pediatric hepatologists. This will be even more important as effective pharmaceuticals become available.
Related blog posts:
Y-C Ling et al. JPGN 2024;79:222–228. Performance of Baveno VII criteria for the screening of varices needing treatment in patients with biliary atresia
Methods: This retrospective study enrolled 48 BA patients (23 females and 25 males) who underwent an esophagogastroduodenoscopy (EGD) and transient elastography at a mean age of 11.18 ± 1.48 years. Transient elastography (Fibroscan® 502 Touch; Echosens) was applied for the LSM assessment in all BA patients recruited in this study.
Clinically-significant portal hypertension (CSPH) of Baveno VI criteria recommend avoiding upper endoscopies for cirrhotic patients with liver stiffness <20 kPa and platelets>150 × 10-9 cells/L (favorable Baveno VI status), and the CSPH of the expanded Baveno VI criteria as the exclusion of subjects with LSM < 25 kPa and platelet count >110 × 10-9 cells/L. (Ref: D Thabut et al. Gastroenterol 2019. Validation of Baveno VI Criteria for Screening and Surveillance of Esophageal Varices in Patients With Compensated Cirrhosis and a Sustained Response to Antiviral Therapy)
CSPH of Baveno VII criteria was defined as LSM ≥ 25 kPa and excluded patients with LSM < 15 kPa and platelet count ≥150 × 10-9 /L. Subjects with LSM between 20 and 25 kPa and platelets <150 × 10-9 /L or LSM between 15 and 20 kPa and platelets <110 × 10-9/L are also defined as CSPH. (Ref: Baveno VII criteria Ref: M Mendizabal et al. Annals of Hepatology; 2024: 29: 101180. Evolving portal hypertension through Baveno VII recommendations)
Key findings:
In the discussion, the authors note that the utility of the Baveno VII criteria for adults. “The real‐world data showed the CSPH defined by Baveno VII criteria predicts a five‐times increase in the risk of liver decompensation in chronic active liver disease patients.”
My take: This study shows that the combination of LSM and platelet counts using the Baveno VI or VII criteria help select patients with BA who need upper endoscopy to screen for varices needing treatment. These criteria also identify patients needing liver transplantation.
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.
S Pandurangi et al. Hepatology 2024; 80: 152-162 Open Access!.Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort
Methods: MMP-7 was measured in serum samples of 399 infants (North America)18 with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays.
Key findings:
In the discussion, the authors note that MMP-7 has performed better in studies with Asian populations, MMP-7 could be useful for dried blood spots in newborns, and could be useful as a measure of successful HPE; continued elevation of MMP-7 has been associated with hepatic fibrosis.
My take: This study shows that MMP-7 is not a perfect assay but often quite helpful. The exact cutoff depends on the specific assay that is utilized. Also, this study shows that checking for A1AT and checking an ultrasound to exclude choledochal cyst need to continue to be done early in the evaluation process.
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.
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