Does Liver Fibrosis Progress Faster in People Who Have HIV When They Acquire Hepatitis C?

		SUMMARY: HIV positive men who subsequently became infected with hepatitis C virus (HCV) appeared to have a suspiciously rapid rate of liver disease progression in the European NEAT study, according to a poster presented at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) this week in San Francisco. The researchers suggested that apparent fast progression might be attributable to short duration of follow-up.

By Liz Highleyman

Over the past decade, researchers have been reporting outbreaks of acute HCV infection among HIV positive men who have sex with men (MSM), first in large cities in the U.K. and Europe, and later in Australia and the U.S.

The natural history of liver disease progression in individuals who already have HIV when they acquire HCV is not fully understood. Daniel Fierer's group at Mt. Sinai School of Medicine in New York has reported alarming levels of fibrosis in men coinfected for only a short time. European investigators, however, have not observed a similar phenomenon.

Martin Vogel and fellow investigators with the NEAT Study Group prospectively evaluated liver fibrosis progression among HIV positive patients with acute hepatitis C.

The researchers estimated extent of fibrosis using the transient elastometry method (FibroScan), which measures liver "stiffness." They used the following stiffness value cut-offs as equivalents of Metavir fibrosis scores:

	< 6 kiloPascals (kPa): stage F1 (mild fibrosis);
	6.1 to 9.0 kPa: stage F2 (moderate fibrosis);
	9.1 to 12 kPa: stage F3 (advanced fibrosis);
	12 kPa: stage F4 (severe fibrosis or cirrhosis).

It was assumed that patients had stage F0 (absent fibrosis) prior to acute hepatitis C, unless available FibroScan or liver biopsy results indicated otherwise. Fibrosis progression rate was calculated by dividing the difference in fibrosis units by the duration of follow-up time.

The study included 30 HIV positive men, 90% of whom were in the MSM HIV transmission risk group. The median age was 39 years. With regard to HIV status, 70% were on combination antiretroviral therapy (ART), with a median exposure duration of 43 months, and the median CD4 count was 444 cells/mm3; 17% each had used didanosine (ddI, Videx) and nevirapine (Viramune), 23% had used stavudine (d4T, Zerit), and 43% had used zidovudine (AZT, Retrovir) -- all drugs that have been linked to liver toxicity in some prior studies.

With regard to HCV status, 80% had hard-to-treat genotype 1, with most of the remainder having genotype 4 (uncommon in Europe outside the MSM coinfection clusters). The median HCV RNA level was 5.9 log. A majority (67%) had elevated ALT, 27% showed some symptoms of acute infection, and 10% developed jaundice (yellowing of the skin and eyes). Half had other liver disease risk factors, including heavy alcohol use (3%), illegal/recreational drug use (33%), diabetes (3%), and lipodystrophy (10%).

Results

	Over a median follow-up period of 0.4 year (4-5 months), the overall calculated fibrosis progression rate was 3.8 Metavir fibrosis units per year.
	Plotting fibrosis progression rate over follow-up time revealed a logarithmic association between observation time and calculated fibrosis progression rate.
	Short observation times were strongly correlated with calculated high fibrosis progression rates.
	There was no observed interaction of risk factors for cirrhosis or ART exposure with follow-up time.
	ALT elevation > 2.5 x upper limit of normal at the time of FibroScan was associated with higher liver stiffness measurements.
	However, limiting the analysis to only patients with ALT below this level produced similar findings.

"Calculated high fibrosis progression rates after acute HCV infection in HIV-positive individuals are probably influenced by short observation periods," the NEAT investigators concluded.

"Higher liver stiffness in the acute phase of HCV infection may be at least partially explained by higher inflammatory activity which has been shown to increase stiffness leading to overestimation of fibrosis," they continued.

Finally, they advised, "A linear model for fibrosis progression, as is currently applied in the setting of chronic HCV infection, should be used with caution in the setting of acute HCV infection."

There is controversy over whether FibroScan is accurate enough to track fibrosis progression. While it performs well at distinguishing mild versus severe liver disease, it is not as good at distinguishing between intermediate stages.

Of note, the Mt. Sinai team's findings are based on liver biopsies, which are still considered the "gold standard" for diagnosing and staging liver disease.

University of Bonn, Germany; Chelsea and Westminster Hospital, London, UK; Practice Mauss/Schmutz/Hegener/Athmann, Düsseldorf, Germany; Practice Dupke/Baumgarten/Carganico, Berlin, Germany.

2/19/10

Reference
M Vogel, E Page, P Holmes, and others (NEAT Study Group). Liver fibrosis progression after acute HCV infection (AHC) in HIV-positive individuals. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 642.