Report from EASL; The European Association for the Study of the Liver Conference, Rotterdam, April 28-May 3, 2000 - Report 2

EASL Day 1 Afternoon Meeting, Rotterdam, April 28-May 3

It's 8pm in Rotterdam. The afternoon's pre-conference session ended and in the walk back to my hotel I observed the aftermath of today's street fair. I think this weekend is also the Queen's celebration in the Netherlands. The partying goes on. The streets around this area are lined with sidewalk cafÈs and it appears to me that few thousand people are still partying, mostly young people, all within a several block radius-- listening to rock music, drinking beer, and dancing. The music is loud, the crowds are big and people are dancing in the streets.

At this afternoon's pre-EASL conference meeting, I had a talk with Thierry Poynard, the author of a study reported at ICAAC '99 in which individual's on a PI HAART regimen showed improved fibrosis. I asked him if the results could have occurred with any antiretroviral regimen without a PI and he said no. He said, they looked at viral load reduction and that was not associated with the fibrosis improvement, but the PI regimen was associated with improved fibrosis. I'll copy that report from ICAAC below.

I asked him in light of that information why does end-stage liver disease appear to be a leading cause of death among people with HIV many of whom are on a PI HAART regimen? He said there are many factors that may affect such an outcome but he stuck with his feeling that the improved fibrosis from a PI HAART regimen is a positive influence. He said many factors need to be considered when selecting a HAART regimen. This raises an important question that should be addressed by studies--PI HAART can raise LFTs and PI HAART improves fibrosis, so how does PI HAART when LFTs are increased affect progression of liver disease as evaluated by liver biopsy?

Liver Fibrosis Progression (this report was taken from NATAP web site and from NATAP Reports Dec. '99 newsletter)

Christine Katlama and others in French HIV research group reported here in Dallas at AASLD Conference and also at ICAAC HIV Conference in September that individuals  co-infected with HIV and HCV who receive protease inhibitor therapy for  HIV can experience decreased liver fibrosis progression rates. What if the 2 patients in German study above were taking protease inhibitors for HIV? The authors here said HCV related liver fibrosis progression is accelerated in HIV infected patients. The objective of their study is to examine the impact of combination anti-retroviral therapy for HIV including a PI on liver fibrosis progression rates. 162 consecutive HCV-HIV coinfected patients (119 male; 36.7 yrs age)  were studied. At liver biopsy, HCV duration was 14.4 years, CD4s were  327, and HIV RNA was performed in 79 patients (17,823 copies/ml). 42  patients had self-recorded alcohol consumption (SRAC above 50g/day). At  liver biopsy, 49 patients were receiving PI therapy for 12 months.

Estimated FPR (fibrosis progression rate) was defined as ratio between fibrosis stage (METAVIR scoring system) and HCV duration. Since the linearity of liver fibrosis progression remains questionable only non-parametric statistical tests were used for univariate and multivariate analysis.

Patients receiving PI therapy had higher duration of HCV infection and lower HIV viral load than patients who had never received PI treatment (17 vs 14 years, p=0.04; 12,154 vs 22,332 copies/ml, p=0.03). Neither CD4 count nor alcohol consumption showed significant difference between the 2 groups. Patients with high FPR (above 2.0 fibrosis units/year; that is, expected time from HCV infection to cirrhosis below 20 years, n=45) included more patients older than 20 years at HCV infection, with a SRAC (alcohol consumption) above 50 g/day, and with a CD4 count below 200, and less patients treated with a PI compared to patients with low FPR (equal to or below 2.0 fibrosis units/year, n=117).

Logistic regression analysis identified 2 independent factors associated with high FPR: CD4 count below 200 (odds ratio=15; p below 0.0001)) and no previous treatment with PI (odds ratio=3.8, p=0.02). The duration of PI therapy is associated with a low FPR in HCV-HIV coinfected patients. The independent association between PI therapy and liver fibrosis progression is not explained by the studied factors, including the CD4 count