Relationship Between Changes in Serum Levels of Keratin 18 and Changes in Liver Histology in Children and Adults With Nonalcoholic Fatty Liver Disease

Vuppalanchi, Raj; Jain, Ajay K.; Deppe, Ross; Yates, Katherine P.; Comerford, Megan; Masuoka, Howard C.; Neuschwander‐Tetri, Brent A.; Loomba, Rohit; Brunt, Elizabeth M.; Kleiner, David E.; Molleston, Jean P.; Schwimmer, Jeffrey B.; Lavine, Joel E.; Tonascia, James; Chalasani, Naga

doi:10.1016/j.cgh.2014.05.010

Cited by 100 publications

(75 citation statements)

References 31 publications

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“…The only prior study with longitudinal data for both ALT and liver histology in children was TONIC 30 . Notably, in TONIC, the change in ALT had an AUROC of 0.79 for predicting histologic improvement in children over 96 weeks 31 . In addition, with every 10 U/L decrease in ALT levels over 96 weeks, children in TONIC had 28% greater odds of histologic improvement.…”

Section: Discussionmentioning

confidence: 98%

In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores

Neuschwander‐Tetri

Natta

Abrams³

et al. 2016

Gastroenterology

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103

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Background & Aims No treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD. Methods We performed a double-masked trial of 169 children with NAFLD Activity Scores ≥ 4 at 10 centers. From June 2012 to January 2014, the patients were randomly assigned to receive CBDR or placebo twice daily (300 mg for ≤65 kg, 375 mg for >65–80 kg, 450 mg for >80 kg) for 52 weeks. The primary outcome from the intention to treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in NAFLD Activity Score ≥ 2 points without worsening fibrosis; patients without biopsies from week 52 (17 in the CBDR group and 6 in the placebo group) were considered non-responders. We calculated relative risks (RR) of improvement using stratified Cochran-Mantel-Haenszel analysis. Results There was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% CI, 0.8–2.1; P=.34). However, children receiving CBDR had significant changes in pre-specified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction of 53±88 U/L vs a reduction of 8±77 U/L in the placebo group; P=.02) and aspartate aminotransferase (reduction of 31±52 vs a reduction of 4±36 U/L in the placebo group; P=.008), and a larger proportion had reduced lobular inflammation (in 36% of patients in the CBDR group vs placebo 21% of patients in the placebo group; RR, 1.8; 95% CI, 1.1–2.9; P=.03). In a post-hoc analyses, of children ≤65 kg, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3–12.3; P=.005). Conclusions In a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR did, however, have significant reductions in serum levels of aminotransferase levels and lobular inflammation. ClinicalTrials.gov no: NCT01529268.

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Section: Discussionmentioning

confidence: 98%

In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores

Neuschwander‐Tetri

Natta

Abrams³

et al. 2016

Gastroenterology

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103

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“…Serum level of ALT is commonly used as a surrogate indicator for evaluating liver histology in various liver diseases, and ALT seems to be more closely associated with steatohepatitis than other biomarkers, e.g. cytokeratin-18 [34]. That is, in elevated ALT group, NAFLD subjects are suspected as suffering from steatohepatitis.…”

Section: Discussionmentioning

confidence: 99%

The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease

et al. 2017

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BackgroundThe triglyceride and glucose index (TyG) has been proposed as a marker of insulin resistance. We aimed to investigate the ability of TyG, through comparing with the predictive value of alanine aminotransferase (ALT), to identify individuals at risk for nonalcoholic fatty liver disease (NAFLD).MethodsA cross-sectional study was conducted in a Chinese health examination cohort of 10 761 people aged above 20 years. NAFLD was diagnosed by ultrasonography.ResultsCompared with the participants in the lowest quartile of TyG, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were 1.8 (1.5–2.1), 3.0 (2.5–3.5), and 6.3 (5.3–7.5) for those in the second, the third, and the fourth quartile of TyG, whereas the corresponding ORs (95% CI) for NAFLD were 1.5 (1.3–1.7), 1.9 (1.6–2.2), and 3.1 (2.6–3.7) for the upper three quartiles of ALT. These results suggested that TyG was superior to ALT in association with NAFLD risk. According to the ROC analysis, the optimal cut-off point of TyG for NAFLD was 8.5 and the area under the ROC curve (AUC) was 0.782 (95% CI 0.773–0.790), with 72.2 and 70.5% sensitivity and specificity, respectively. The AUC of TyG was larger than that of ALT (0.715 (95% CI 0.705–0.725), P for difference <0.0001), whereas the largest AUC was obtained when adding TyG to ALT (0.804 (95% CI 0.795–0.812), P for difference <0.0001).ConclusionsTyG is effective to identify individuals at risk for NAFLD. A TyG threshold of 8.5 was highly sensitive for detecting NAFLD subjects and may be suitable as a diagnostic criterion for NAFLD in Chinese adults.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0409-6) contains supplementary material, which is available to authorized users.

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“…The durability of these histologic changes in children is unknown. Decrease in ALT is commonly used as a surrogate marker of improvement in histology of NAFLD, as there is some evidence to support its use in pediatric clinical trials (19, 77). While an ALT at a single time-point has poor correlation to phenotype, a decrease in ALT of 10 U/L over 96 weeks is associated with 1.28 relative odds of improvement in histology and 1.37 relative odds of resolution of NASH (77).…”

Section: Treatment Of Nafld In Childrenmentioning

confidence: 99%

NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children

Vos

Abrams

Barlow

et al. 2017

J. pediatr. gastroenterol. nutr.

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737

846

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Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs in the setting of insulin resistance and increased adiposity. It has rapidly evolved into the most common liver disease seen in the pediatric population and is a management challenge for general pediatric practitioners, subspecialists and for health systems. In this guideline, the expert committee on NAFLD (ECON) reviewed and summarized the available literature, formulating recommendations to guide screening and clinical care of children with NAFLD.

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Relationship Between Changes in Serum Levels of Keratin 18 and Changes in Liver Histology in Children and Adults With Nonalcoholic Fatty Liver Disease

Cited by 100 publications

References 31 publications

In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores

In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores

The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease

NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children

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