Three Factors Predictive of ALT > 5 times Upper Limit of
Normal: HBV, HCV and elevated baseline ALT; 45% with HBV & 33% with HCV had
ALT > 5 times Upper limit of Normal
In this January issue of AIDS, a research group from the
Netherlands reported on a study to investigate the risk of hepatotoxicity after
starting a protease inhibitor HAART regimen with and without hepatitis B and C.
This is a retrospective study of 394 HIV-infected patients at one university
site in Amsterdam.
The primary aim of this retrospective study was to
investigate whether chronic HBV or HCV is a risk factor for LEE (liver enzyme
elevation) which was defined for this study as ALT or AST at least 5 times the
upper limit of normal and an absolute increase of >100 U/I. The secondary aim
was to estimate the risk of LEE following the initiation of HAART, and to
identify other potential risk factors which might enhance the risk. Thirdly, to
describe the effect of continuing or changing the HAART regimen on the course of
394 patients with HBV & HCV known status were
followed for median of 16 months (8-21). Of the 394, 29 (7%) were HbsAg
positive, 14% (57) were antibody C positive, and two were both HbsAg positive
and HCV antibody positive. Authors reported that patients did not differ
significantly between the three hepatitis serologic subgroups, except for sex,
risk group for HIV transmission, and ALT, AST, y-GT, and AF values (Table 1).
Patients with chronic hepatitis had a higher risk for LEE compared with patients without co-infection: 37% vs 12%.
45% with HBV and 33% with HCV had LEE
70 (18%) out of the 394 developed LEE; 13 out of 29
(45%), and 19 out of 57 (33%) out of the patients who were HbsAg positive or HCV
positive, respectively, compared with 38 out of
306 (12%) among subjects without HCV or HBV. The two patients with
HBV+HCV did not develop LEE.
The 70 cases of LEE occurred a median of 25 weeks after starting HAART.
By multivariate analysis, 3 factors were predictive of LEE. The presence of HBV was associated with increased relative risk for LEE of 2.78, and for those with HCV it was 2.46 (p=0.001). Baseline ALT was also a predictor with relative risk of 1.05 per 10 U/I increase in baseline ALT (p=0.0001).
Individuals either continued on their regimen after LEE or changed therapy. In patients with LEE, ALT/AST declined whether HAART was continued or modified.
Patients were using 1 of 4 PI regimens (ritonavir, indinavir, RTV/SQV, saquinavir) and none was predictive of LEE.
Overall, ALT & AST values decreased in all patients 90 days after LEE developed. But they decreased more in patients who modified treatment than in those who did not (Table 3).
Most ALT & AST normalized 90 days after LEE
when patients modified treatment except for those with HCV. The ALT in the HCV
group did not differ whether patient continued or modified regimen. 48 weeks
later, in general, AST & ALT returned to baseline in those who modified
treatment. And to just above baseline in those who continued on same treatment.
But I could not find the 48 week outcome for those with HCV in this study.
Continuation of treatment for those with LEE: ALT
242; 90 days after modification later: ALT 101. For those with HCV: 359 ALT; 90
days later: 134. Those with HBV reduced ALT 90 days later from 205 to only 147.
Modification of treatment for those with LEE: ALT
224; 90 after modification: ALT 40. For those with HCV: 215; 90 after
modification: 138. Those with HBV had ALT reduced from 533 to 43.