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When the TRMOD approach was applied to fold baseline ALT and bilirubin data, an ALT limit of 6.9× baseline and a bilirubin limit of 6.5× baseline was calculated from oncology clinical trials (see figure 13 in [ 25]).
Two additional Cox models examined only the TPV/r patients in RESIST 1 and 2, and compared the risk of DAIDS Grade 3/4 ALT and/or AST elevation in patients who were either HBV/HCV co-infected or who had DAIDS Grade ≥2 for ALT and/or AST at baseline versus those patients who had neither co-infection nor baseline ALT and/or AST elevation.
Males with baseline ALT of 200 UL/L are three times more likely to develop a reactivation than people with lower levels.
Of the 1831 patients on NVP at baseline, 1444 (79%) patients had a baseline ALT measurement.
Analyses were also performed according to gender and BMI, in the subgroup of patients without coinfection with Delta, HIV or HCV, and in patients with normal baseline ALT.
Biochemical evidence of hepatitis was recorded when the serum ALT concentration exceeded the baseline ALT level by more than two-fold, as defined by a peak ALT value that was equal to or greater than twice the pre-challenge values.
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Additionally, TRMOD was applied to the aggregated oncology data to examine fold-baseline ALT and total bilirubin, indicating outlier detection limits of ALT 6.9 × baseline and bilirubin 6.5 × baseline [ 23].
Seroconversion rates were further enhanced in patients with elevated pretreatment ALT, reaching 60% by 3 years in those with baseline ALT>2 × ULN.
The increase in ALT was unrelated to the change in waist circumference but tended to correlate with the weight increase (ratio of ALT at study end/baseline ALT to the increase in weight, r = 0.42, p = 0.085).
Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006).
Increased frequency of monitoring should be considered when TPV/r is administered to patients with elevated baseline ALT/AST levels, or active HBV/HCV co-infection, as these patients may be at increased risk for developing further transaminase elevations.
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