HCV, Liver Enzyme Test (ALT) and the Biopsy
"80%
(8/10) of co-infected patients for whom biopsy may have been deemed
inappropriate based on normal ALT levels had significant liver pathology
consistent with chronic HCV infection", M.
Hoffman-Terry, MD
In a
small study presented at ICAAC and titled "Correlation of ALT with Degree
of Liver Damage by Biopsy in HCV/HIV Co-infected Adults", Dr. Hoffman-Terry
reports 8/10 co-infected individuals with normal ALT had biopsy proven
inflammation/fibrosis. As well, all 14 patients with abnormal ALT had biopsies
revealing inflammation with or without fibrosis. The number of individuals in
the study was not large enough to achieve statistical significance.
This
study was intended to evaluate the advisability of utilizing ALT (alanine
aminotransferase) elevation as the basis for recommending liver biopsy in adults
coinfected with HIV and HCV. But the study findings suggest that ALT may not be
a reliable indicator for whether or not a biopsy should be performed.
24
coinfected patients in Dr Hoffman-Terry's clinic outside of Philadelphia in
Allentown, PA who had stable HIV and detectable HCV viral loads were offered
liver biopsy, regardless of ALT level. Ultrasound guided liver biopsies were
performed and graded 0-IV (Scheuer grading system) based on degree of
inflammation/fibrosis. Patients were excluded for active alcohol or injectable
drug use or for other possible causes of hepatitis. 14 individuals had abnormal
and 10 had normal ALTs. 58% were Hispanic. Age, sex, and racial breakdown were
similar in both groups. 33% were female with a mean age of 41.
Mean CD4
count was lower in the normal ALT group (342 vs. 512). 70% of the normal ALT group versus 50% of the abnormal group had
undetectable HIV viral loads <50 copies/ml. We need larger studies to
address HCV progression in coinfected persons with undetectable HIV viral load
and various CD4 counts. Does CD4 nadir (lowest CD4 count a person has ever had)
indicate reduced capacity to respond to HCV therapy?
Mean CD4
was 442 and 58% had undetectable HIV viral loads at <50 copies/ml. 83% were
on antiretroviral HIV therapy with 85% of those on HAART and 15% on dual nukes.
70% had HCV viral loads >1 million copies/ml. Of the 10 with normal ALTs, 8
had positive biopsies (with inflammation/fibrosis) with 2/8 showing severe
inflammation+/-fibrosis.
Here are
the HIV regimens for the 10 individuals with normal ALT:
D4T+Nevirapine+Abacavir
Abacavir+nevirapine+amprenavir+fortovase
D4T+3TC+nelfinavir
D4T+3TC+nelfinavir
D4T+3TC+indinavir
No
treatment
D4T+3TC+nelfinavir
D4T+3TC
AZT+efavirenz
D4t+3TC+indinavir
While demographics, HCV and HIV viral loads, and medication regimens were similar between the two groups, CD4 counts were lower in the normal ALT group. The author suggests that maybe advancing HIV immunosuppression makes it more difficult to mount an inflammatory response to HCV infection with subsequent release of ALT into the liver and bloodstream. We need to find tests that can help identify which patients need biopsy and treatment consideration. I think that everyone with HIV and HCV should get a biopsy as soon as they know they are coinfected to properly consider HIV and HCV treatment options. Some individuals may have cirrhosis or more advanced HCV and you may not know it without biopsy. Some individuals may have had HCV for many years. It's important for a doctor to know how long a person has been using IV drugs so they can estimate the length of time a person may have HCV. HCV is easier to transmit than HIV and the odds are that a person may contract HCV early in their use of IV drugs.