By Liz Highleyman

Liver steatosis, or accumulation of fat in liver cells, can have a variety of causes including viral hepatitis, heavy alcohol use, and drug toxicity. It is increasingly recognized as a component of the metabolic syndrome, a set of related conditions including insulin resistance, abdominal obesity, and blood lipid abnormalities.

Past research has indicated that steatosis appears to contribute to liver fibrosis, cirrhosis, and possibly hepatocellular carcinoma, but this association is not fully understood.

As reported in the February 5, 2009 advance online edition of the Journal of Viral Hepatitis, T.J. Cross from Derriford Hospital in Plymouth, U.K. and colleagues performed a retrospective analysis to assess whether steatosis influences fibrosis progression.

The analysis included 112 patients with chronic hepatitis C virus (HCV) infection who underwent 2 liver biopsies with a median interval of 50 months. A majority were men and the median age was 44 years. Participants were not treated for hepatitis C because they had mild fibrosis, declined therapy, or had coexisting disease precluding treatment.

Fibrosis was staged using the Ishak system (F0-F6) and steatosis was staged using the Kleiner system (S0 = < 5% of liver cells affected; S1 = 5%-33%; S2 = 33%-66%; and S3 = > 66%).

Results

On the first liver biopsy, 60 patients (54%) had stage S0 steatosis, 34 (30%) had stage S1, 12 (11%) had stage S2, and 6 (5%) had stage S3.

Steatosis was associated with having HCV genotype 3 (odds ratio 4.8; P = 0.02).

23 patients (21%) experienced fibrosis progression by the second biopsy, defined as an increase of at least 1 Ishak stage.

In a univariate analysis, fibrosis progression was associated with older age (P = 0.004), higher aspartate transaminase (AST) level (P = 0.04), and baseline steatosis (P = 0.005).

In a multivariate analysis, however, only baseline steatosis remained a significant risk factor (odds ratio 14.3; P = 0.006).

In a Kaplan-Meier analysis, steatosis influenced time to progression to significant fibrosis (F3 or higher) and cirrhosis (F5-F6) (P = 0.001 and P = 0.049, respectively).

"The finding that steatosis was significantly associated with fibrosis progression indicates that, independent of baseline fibrosis stage, patients should be considered for antiviral treatment if steatosis is present," the study authors concluded.

Furthermore, they added, "strategies to reduce steatosis may have a beneficial effect on fibrosis progression and, therefore, patient outcome."

3/31/09

Reference
TJ Cross, A Quaglia, S Hughes S, and others. The impact of hepatic steatosis on the natural history of chronic hepatitis C infection. Journal of Viral Hepatitis. February 5, 2009 [Epub ahead of print].