End-Stage
Liver Disease in HIV/HCV Coinfected Patients in France By
Liz Highleyman Among
HIV negative individuals with chronic hepatitis C virus (HCV) infection, antiviral
therapy that produces a sustained virological response (SVR) helps prevent progression
to advanced liver disease. The
natural history of hepatitis C progression in HIV/HCV coinfected patients is less
well known. Most studies indicate that coinfected individuals experience more
rapid progression of liver fibrosis (although this may be less likely among those
with well-controlled HIV), and they are less likely to respond to interferon-based
therapy.  The
XVI International AIDS Conference, held last week in Toronto, featured few presentations
on HIV/HCV coinfection. One, presented by Firouzé Bani-Sadr, MD, looked
at progression to advanced liver disease among coinfected patients in France.
The researchers
prospectively followed 248 HIV/HCV coinfected participants from a randomized controlled
trial (RIBAVIC) who received pegylated interferon or conventional interferon,
both with ribavirin, for 48 weeks. The median follow-up time was 30 months. End-stage
liver disease (ESLD) was defined as: 
Liver decompensation (e.g., ascites, severely elevated bilirubin, hepatic encephalopathy,
bleeding esophageal varices);
Hepatocellular carcinoma (HCC);
Liver transplantation;
Liver-related death.
Results
At baseline, the average age was 42 years, 75% were men, 77% had a history of
injection drug use, 59% had HCV genotypes 1 or 4, and 41% had genotypes 2 or 3.
81% were on HAART, 53% had HIV viral loads below 200 copies/mL, and the mean CD4
cell count was 567 cells/mm3.
The mean Metavir fibrosis score at baseline was 2.2, and 35% of patients had stage
F3-F4 fibrosis.
29% of patients overall achieved SVR with antiviral therapy.
17 ESLD-defining events occurred in 9 patients (4%), for an incidence rate of
2.8 per person year (PY); 6 of these patients died of liver-related causes and
2 of non-liver-related causes.
All these events occurred in patients without SVR, who had an ESLD incidence rate
of 3.9% per PY.
All but one event occurred in patients with stage F3-F4 fibrosis at baseline,
who had an incidence rate of 7.4 per PY.
After 3 years, 93% of non-responders remained free of ESLD, compared with 100%
of patients who achieved SVR (P = 0.051).
88% of patients who started with stage F3-F4 fibrosis remained free of ESLD, compared
to 98% of those with stage F1-F2 (P = 0.007).
However, ESLD did not occur in 25 patients with baseline F3-F4 fibrosis who cleared
HCV.
Independent risk factors for ESLD were:
- Stage F3-F4 fibrosis at baseline
(P < 0.001);
- CD4 cell count below 350 cells/mm3 (P = 0.022);
- Lack
of sustained response to anti-HCV therapy (P = 0.068).
Conclusion
The researchers
concluded that, "Our study confirms that the rate of spontaneous hepatic
decompensation in HIV/HCV coinfected patients with asymptomatic cirrhosis is higher
(7.4% per year) than in HCV monoinfected patients (3-4% per year)." However,
they also said that, "Extensive fibrosis or cirrhosis are associated with
[ESLD] events which disappear in HIV/HCV coinfected treated patients with sustained
virological response." As
noted, no cases of ESLD were observed in coinfected patients with achieved SVR,
even if they started treatment with advanced fibrosis. These
results offer reassuring evidence that effective treatment of hepatitis C benefits
HIV/HCV coinfected patients, as it does those with HCV alone. More research is
needed to determine whether interferon maintenance therapy can help reduce the
risk of liver disease progression even among patients who do not achieve SVR. 8/21/06 Reference
F
Carrat, P Cacoub, S Pol, and others. Three years assessment of the risk of end-stage
liver disease in HIV/HCV co-infected patients treated for a chronic HCV infection.
XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract TUAB0301. 
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