SUMMARY: A study from Spain adds to the evidence that liver fibrosis due to hepatitis C virus (HCV) infection may progress unusually fast in people with HIV. However, the investigators reported at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco, effective antiretroviral therapy (ART) that suppresses HIV and raises CD4 cell count reduces the risk of liver disease progression.

By Liz Highleyman

Past research has shown that liver disease typically progresses more rapidly in HIV/HCV coinfected people compared to those with hepatitis C alone, but studies may not be directly comparable and data have not always been consistent.

To shed more light on this issue, Juan Macias and colleagues from several centers in Spain used the transient elastography (FibroScan) method to assess liver fibrosis progression in HIV/HCV coinfected people who were not undergoing treatment for hepatitis C.

Increased fibrosis progression has been observed in studies of HIV/HCV coinfected patients using serial liver biopsies, the researchers explained as background. But because they are invasive, expensive, and uncomfortable, sequential biopsies are not routine, and individuals usually only receive them if disease progression is suspected; thus, serial biopsy recipients are likely not representative of the coinfected population as a whole.

FibroScan uses ultrasound to measure live "stiffness," which is used to estimate fibrosis stage. Though not as accurate as biopsies (especially at distinguishing between intermediate stages), FibroScan is non-invasive and simpler, making it feasible to offer serial fibrosis assessments for all patients.

In this prospective study, liver stiffness was measured at baseline with follow-up measurements at least every 12 months. Fibrosis stages were classified as follows:

	Stage F0-F1 (absent to mild fibrosis): < 6 KiloPascal (KPa);
	Indeterminate stage: 6.1 to 8.9 KPa;
	Stage > F2 (significant fibrosis): > 9 KPa
	Stage F4 (cirrhosis): > 14.2 KPa.

The analysis included 441 HIV/HCV coinfected patients with follow-up values. Most (80%) were men and the median age was 44 years. Almost all (97%) were receiving combination ART during follow-up. At baseline, the median CD4 count was 444 cells/mm3 and 74% had undetectable HIV viral load. About three-quarters had hard-to-treat HCV genotypes 1 or 4, about 20% had received previous anti-HCV therapy, about 6% also had hepatitis B, and the median liver stiffness at baseline was 6.9 KPa.

Results

	Among 179 individuals with FibroScan measurements at 18-24 months, the following changes in fibrosis classification were observed:
	16% showed fibrosis regression; 54% showed no change; 30% progressed by at least 1 liver stiffness category (including 4% who progressed by 2 categories);
	Among the same individuals, the following changes in liver stiffness were recorded:
	17% had > 20% decrease in liver stiffness; 46% had no change in liver stiffness; 37% had > 20% increase in liver stiffness.
	In a multivariate analysis, the following factors were associated with changes of at least 1 liver stiffness category during follow-up:
	CD4 cell gain of at least 50 cells/mm3 during follow-up: adjusted odds ratio/mL (OR) 0.33; Maintaining undetectable HIV viral load (< 50 copies/mL) during follow-up: adjusted OR 0.42.

Based on these findings, the researchers concluded, "Achievement of HIV suppression and increase of CD4 cell counts with HAART is associated with a lower risk of worsening of liver damage."

However, they added, "in spite of effective HAART, liver fibrosis progresses in a significant proportion of HIV/HCV coinfected patients over a short period of time."

Hosp Univ de Valme, Seville, Spain; Hosp de Donostia, San Sebastian, Spain; Hosp Univ Reina Sofia, Cordoba, Spain; Hosp de la Linea, Cadiz, Spain; Hosp Juan Ramon Jimenez, Huelva, Spain; Hosp Univ Virgen de la Victoria, Malaga, Spain; Hosp Univ Puerto Real, Cadiz, Spain; Hosp Univ Carlos Haya, Malaga, Spain.

3/2/10

Reference
J Macias, M von Wichmann, A Rivero, and others. Fast Liver Damage Progression in HIV/HCV-co-infected Patients in Spite of Effective HAART. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. (Abstract 659).