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Optimized cutoffs of gamma-glutamyl transpeptidase-to-platelet ratio, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 scoring systems for exclusion of cirrhosis in patients with chronic hepatitis B.

ABSTRACT: Accurate prediction of the extent of fibrosis is of great clinical importance in patients infected with chronic hepatitis B (CHB). This study aimed to compare the performance of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in evaluating liver fibrosis stages and to identify optimized cutoffs to exclude cirrhosis. Consecutive patients with CHB with liver biopsies were enrolled and randomly divided into derivation and validation cohorts. Areas under the receiver operating characteristic curve were used to evaluate the diagnostic performance of APRI, FIB-4, and GPR to distinguish fibrosis stages. New cutoffs with a sensitivity of at least 90% and a negative predictive value (NPV) of more than 95% were identified. A total of 880 individuals were enrolled in this study. The derivation data set consisted of 617 patients, with 82 patients with cirrhosis. In the validation cohort (n = 263), 29 patients had cirrhosis. APRI, FIB-4, and GPR had comparable diagnostic performance for diagnosing significant fibrosis. GPR outperformed APRI (p < 0.05) in the prediction of cirrhosis. A newly identified GPR score of 0.35 had a sensitivity and NPV of 93.9% and 98.0%, respectively, and misclassified 5 of 82 (6.1%) patients with cirrhosis in the derivation group. All new cutoffs identified in this study also reached our goal in the validation cohort. The new GPR score could rule out a larger proportion of individuals without cirrhosis, and the subgroup analysis showed more stable performance. However, the lower cutoff dose increases the need for further testing compared to the conventional cutoff. Conclusion: A newly identified cutoff for GPR (<0.35) could rule out more patients without cirrhosis compared to APRI and FIB-4 and have low misclassification rates.

SUBMITTER: Liu X

PROVIDER: S-EPMC9234683 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsPredictive, noninvasive tools are needed to monitor key features of nonalcoholic fatty liver disease (NAFLD) in children that relate to improvement in liver histology. The purpose of this study was to evaluate the relationship between liver chemistries and liver histology using data from the CyNCh (Cysteamine Bitartrate Delayed-Release for the Treatment of NAFLD in Children) clinical trial.Approach and resultsThis study included 146 children. Improvement in liver histology, defined as decrease in nonalcoholic fatty liver disease (NAFLD) Activity Score ≥2 points without worsening of fibrosis, occurred in 43 participants (30%). There were 46 participants with borderline zone 1 nonalcoholic steatohepatitis (NASH) at baseline, with resolution in 28% (12 of 46). Multivariate models were constructed using baseline and change in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at 52 weeks, for improvement in (1) liver histology primary outcome, (2) borderline zone 1 NASH, and (3) fibrosis. For improvement in histology, the model (P < 0.0001) retained baseline and change in GGT (area under the receiver operating characteristic [AUROC], 0.79; 95% confidence interval [CI], 0.71-0.87). For borderline zone 1 NASH, the model (P = 0.0004) retained baseline and change in ALT (AUROC, 0.80; 95% CI, 0.67-0.93). For fibrosis, the model (P < 0.001) retained baseline and change in ALT (AUROC, 0.80; 95% CI, 0.67-0.93). Additional clinical parameters were added to the models using Akaike's information criterion selection, and significantly boosted performance: improvement in histology with AUROC of 0.89 (95% CI, 0.82-0.95), borderline zone 1 NASH with AUROC of 0.91 (95% CI, 0.83-0.99), and fibrosis with AUROC of 0.89 (95% CI, 0.82-0.94). Models were validated using data from the TONIC (Treatment of Nonalcoholic Fatty Liver Disease in Children) trial.ConclusionsIn children with NAFLD, dynamic changes in serum ALT and GGT are associated with change in liver histology and appear to be powerful indicators of histological response.

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Optimized cutoffs of gamma-glutamyl transpeptidase-to-platelet ratio, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 scoring systems for exclusion of cirrhosis in patients with chronic hepatitis B.

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