Liver Disease Progression in HIV/HCV Coinfected People

By Liz Highleyman

A number of studies have shown that HIV positive people with hepatitis C virus (HCV) coinfection tend to experience more rapid liver disease progression than people with hepatitis C alone -- though just how much more rapid remains subject to controversy.

One factor that may help explain conflicting study findings is that outcomes may differ depending on whether investigators evaluate liver damage according to liver biopsies or transient elastography (FibroScan), which uses sound waves to measure liver "stiffness."

As reported in a poster presented at the European Association for the Study of the Liver's International Liver Congress (EASL 2011) this month in Berlin, T.M. Vu and colleagues from Johns Hopkins looked at the relationship between clinical outcomes and liver stiffness measurement in HIV/HCV coinfected adults.

Liver stiffness has been shown to correlate with histological stages (for example Metavir fibrosis stages F0 through F4), the researchers noted as background, but the degree to which liver stiffness predicts clinical outcomes is not clear. Transient elastography is generally better at distinguishing absent or mild fibrosis from advanced fibrosis or cirrhosis than it is at distinguishing between intermediate stages.

Nearly 300 HIV/HCV coinfected patients at the Johns Hopkins HIV clinic underwent liver stiffness measurement between 2005 and 2009. About two-thirds of participants were men, 88% were black, the median age was 50 years, and about 75% had a history of injection drug use. Overall they had well-controlled HIV disease, with a median CD4 cell count of 420 cells/mm3 and 75% with HIV viral load < 400 copies/mL.

Transient elastography was performed by experienced technicians. No fibrosis was defined as a liver stiffness measurement of < 8.0 kiloPascals (kPa), fibrosis was defined as 8.0-12.3 kPa, and cirrhosis was defined as > 12.3 kPa.

The researchers prospectively followed participants for a median of just under 2 years to evaluate clinical outcomes including hepatocellular carcinoma (HCC), end stage liver disease (ESLD), and death due to any cause. Outcomes were abstracted from medical records and the National Death Index.

Results

	The median liver stiffness at baseline was 8.3 kPa.
	Based on transient elastography results, 49% of participants had no fibrosis, 27% had fibrosis, and 24% had cirrhosis.
	Incidence rates of HCC, ESLD, or all-cause mortality varied according to liver stiffness classification:
	< 8.0 kPa: 14.9 per 1000 person-years; 8.0-12.3 kPa: 32.6 per 1000 person-years; >12.3 kPa: 75.8 per 1000 person-years.
	In a multivariate analysis, factors independently associated with greater risk of HCC, ESLD, or death were:
	Liver stiffness > 12.3 kPa (incidence rate ratio 3.9, or about a 4-fold higher risk); Age > 50 years (incidence rate ratio 4.5).
	Conversely, having a CD4 cell count > 350/mm3 was protective against these clinical outcomes (incidence rate ratio 0.1).

Based on these findings, the researchers concluded, "In HIV/HCV coinfected adults, liver stiffness was independently associated with increased risk of important clinical outcomes, including liver failure and death."

"These data validate liver stiffness measurement as a prognostic marker," they added, "and suggest the potential role of liver stiffness measurement for clinical decision-making related to treatment and HCC screening."

Investigator affiliation: Johns Hopkins University School of Medicine and Johns Hopkins University School of Public Health, Baltimore, MD.

4/12/11

References
TM Vu, C Sutcliff, S Mehta, et al. Baseline liver stiffness measured by transient elastography is independently associated with risk of end-stage liver disease and death among HIV/HCV co-infected adults. 46th Annual Meeting of the European Association for the Study of the Liver (EASL 2011). Berlin. March 30-April 3. Abstract 1069.