A179 FEATURES OF THE METABOLIC SYNDROME ARE ASSOCIATED WITH LACK OF SERUM ALT NORMALIZATION DURING THERAPY FOR CHRONIC HEPATITIS B
Bibliographic record
Abstract
Despite complete suppression of HBV DNA with antiviral agents, serum alanine aminotransferase (ALT) levels fail to normalize in some patients with chronic hepatitis B (CHB). Our objective was to evaluate factors associated with persistent ALT elevation during treatment with tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate(TDF). Adults with CHB enrolled in two Phase 3 studies of TAF 25 mg QD vs. TDF 300 mg QD (Study GS-US-320-0108 in HBeAg- and GS-US-320-0110 in HBeAg+ subjects) were included. Rates of ALT normalization at Weeks 12 and 48 were determined using reference ranges recommended by AASLD (≤19 U/L for women, ≤30 for men). A sensitivity analysis examined ALT normalization according to central laboratory (Covance) criteria (<69 yrs:≤34 U/L for women, ≤43 for men; ≥69 yrs: ≤32 U/L for women, ≤35 for men). Associations between host, viral and treatment-related factors, including virologic suppression (HBV DNA <29 IU/mL; Roche COBAS Taqman), with persistent ALT elevation at Week 48 were determined using logistic regression. Based on AASLD criteria, 1,276 of 1,301 subjects (98%) had abnormal baseline (BL) ALT. Median BL ALT and HBV DNA were 82 U/L (IQR 56–126) and 7.4 log10 IU/mL (IQR 5.8–8.3), respectively. Compared with patients treated with TDF, ALT normalization by AASLD criteria at Week 12 (11% vs. 18%; P=0.003) and Week 48 (36% vs. 49%; P<0.001) were more common among patients treated with TAF. Similarly, ALT normalization by central laboratory criteria was greater in TAF vs. TDF-treated subjects at Week 12 (43% vs. 35%; P=0.015) and Week 48 (78% vs. 72%; P=0.012). Patients with elevated ALT at Week 48 had a higher prevalence of overweight (45% vs. 29%; P<0.001), hypertension (15% vs. 10%; P=0.007), dyslipidemia (11% vs. 6%; P=0.003), and diabetes (8% vs. 5%; P=0.062) compared with those with normal ALT. In a multivariate analysis, TAF treatment (odds ratio [OR] 0.60; 95% CI 0.44–0.82; P=0.002) and virologic suppression (OR 0.33; 0.22–0.49; P<0.001) were associated with a lower likelihood of ALT elevation at Week 48. Additional independent predictors of ALT elevation included female sex (OR 1.79; 1.29–2.47; P<0.001), higher BMI (OR 1.14; 95% CI 1.09–1.19; P<0.001), diabetes (OR 2.27; 1.11–4.63; P=0.024), cirrhosis (OR 2.64; 1.53–4.57; P<0.001), and lower BL ALT (OR 0.995; 95% CI 0.993–0.997; P<0.001). In patients with CHB, treatment with TAF compared with TDF is associated with a greater likelihood of ALT normalization independent of virologic suppression. Patients with metabolic risk factors are less likely to normalize ALT, which could occur due to underlying hepatic steatosis. Gilead Sciences, Inc.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".