YVES BENHAMOU,1 VINCENT DI MARTINO,1 MARIE BOCHET,1,4 GENEVI` EVE COLOMBET,2 VINCENT THIBAULT,3 AM´ ELIE LIOU,2 CHRISTINE KATLAMA,4 AND THIERRY POYNARD 1 FOR THE MULTIVIRC GROUP
(HEPATOLOGY August 2001;34:283-287)
ABSTRACT:
Hepatitis C virus (HCV)-related
liver fibrosis progression is accelerated in human immunodeficiency virus
(HIV)-in-fected patients. The effect of protease inhibitor (PI) therapy on liver
fibrosis is unknown. The aim of this work was to analyze the impact of PI
therapy on HCV-related liver fibrosis in HIV/HCV coinfected patients. We
evaluated in a long-term follow-up retrospective cohort study the influence of
In Table 1 below you can see that less patients receiving a PI regimen used more than 50 grams per day of alcohol (20.6% vs 31.9%). This difference may not be significant but raises a question. It's possible this could effect the PI recipients in developing less fibrosis or in having a lower rate of liver progression. As well, I mention below how viral load above or below 200 may play a role in progression of liver disease. I spoke to one of the article's author who said viral load was not an independent risk factor. In other words, according to his statistical analysis viral load did not affect progression. I brought attention to this point because at the DDW Conference this past Summer (2001) a study from Sterling suggested that patients with undetectable HIV viral load were more likely to have cirrhosis.
I think that Benhamou's conclusion is a very soft statement, and this is
appropriate. The sample size is somewhat small, but more importantly the
main problem is that which occurs with retrospective data. There may be
some bias that we can't appreciate in the data.
The patient's that had not received PIs had more fibrosis and possibly
more inflammation on biopsy than the patients that had received some PI
regime but it is impossible to know if this is at all related to the
medications. Perhaps the PI based group would have looked healthier
regardless. The patients that are more ill from liver disease (appear
cirrhotic, complain more of RUQ pain etc) may have been less likely to be
placed on a PI based regime because the provider was nervous about the
issue of PIs in liver disease. Also, we don't know enough about the
cocktails, how they varied. The sample size is not large enough to rule out
all of these things.
Having said that, this study was well done, compared to other studies on the same question. Still, in my opinion, none of these studies have been done very well, well enough to reach fairly firm conclusions. HAART may accelerate HCV progression for some individuals and not for others. This may depend on a number of factors we have yet to identify. (see this article)
I think that we need to see more data. To better assess the
affect of HAART or antiretroviral therapy on HCV disease we need data from
trials comparing various treatment combinations and almost every trial
requires a biopsy on entry and always a medication history. Therefore, we
can see if their HAART correlates with
their pre-HCV treatment stage of disease.
A prospective randomized trial would be ideal but probably not practical
or ethical. I don't think that you can randomize someone to receive or not
receive a certain HAART regime based on their HCV......HIV course drives
this decision.
The mechanisms involved
in the beneficial impact of PI therapy on liver fibrosis remained unknown.
Improvement of immune functions assessed by increases in CD4 count related to
antiretroviral therapy might reduce the liver fibrosis pro-gression rate.
However, in the present study, the influence of PI therapy was independent of
both the CD4 cell count and HIV plasma load. Nevertheless, numerous immune
modifica-tions, other than the increases in CD4 cell count, could have
influenced liver fibrosis progression. Changes in intrahepatic
Tables 3 & 4 show that
having HIV viral load <200 may play a role in liver disease progression.
