Serum fibrosis markers correlate with liver fibrosis stage in patients with advanced chronic hep C

Liver biopsy is currently considered the best way to assess the stage and severity of chronic liver disease. However, it is limited by sampling error, understaging and variability in interpretation. Also, because of its risks, inconvenience and costs, it isn’t practical to use to follow disease progression and treatment effects. As a result, researchers have been trying to develop less invasive tests that can accurately predict disease stage and fibrosis progression.

Researchers led by Robert Fontana of the University of Michigan Medical School examined a panel of serum fibrosis markers along with routine laboratory tests for their ability to estimate cirrhosis in a cohort of patients with advanced hepatitis C. They included 513 patients enrolled in the HALT-C trial, a prospective multi-center NIH study of extended peginterferon therapy for patients with hepatitis C and advanced fibrosis who were non-responders to prior antiviral therapy.

Fontana and his colleagues aimed to determine the utility of a panel of serum fibrosis markers including serum PIIINP, TIMP-1, HA, and YKL-40 in estimating initial disease stage in the subjects by comparing the markers with each patient’s Ishak fibrosis score from liver biopsy. They also examined the relationship between the serum fibrosis markers and hepatic collagen content as measured by computerized morphometry.

“On univariate analysis, nearly all of the tested variables were independent predictors of cirrhosis,” the authors report. They then conducted multivariate analyses and created a model that included TIMP-1, log HA and platelet count. “The 3-variable model was significantly better than any of the individual serum fibrosis markers alone in estimating the presence of cirrhosis,” they write. The model had an area under the receiver operating curve of 0.81 and was better at predicting cirrhosis than other published models.

The model would have correctly categorized 153 HALT-C patients as having a low likelihood of cirrhosis with 86% accuracy. An additional 146 subjects would have been categorized as having a high likelihood of cirrhosis with 73 % accuracy.

The serum fibrosis markers also correlated with the collagen content of biopsy samples, however not as closely as they did with the Ishak fibrosis scores. This suggests that the serum fibrosis markers more closely reflect the pattern of fibrosis determined by standard light microscopy than the quantity of hepatic collagen determined by computerized morphometry.

The study was limited by the unique nature of the HALT-C patient population and by the fact that the models were not tested in an external validation cohort. Still, the researchers conclude, “on multivariate analysis, a 3-variable model consisting of TIMP-1, HA, and platelet count distinguished patients with non-cirrhotic CHC from those with cirrhosis. Also, this new model performed significantly better than other models based on routine laboratory tests, suggesting that serum fibrosis markers provide useful, incremental information in estimating disease stage in CHC.”

Source: Wiley

MRI predicts liver fibrosis, study says
Moderate to severe chronic liver disease can be predicted with the use of diffusion-weighted MRI (DWI), according to a recent study conducted by researchers at New York University Medical Center in New York, NY.
Noninvasive ways to assess liver disease
Two new studies examine non-invasive ways to determine liver fibrosis and cirrhosis. An enhanced version of the Original European Liver Fibrosis panel was found to have good diagnostic accuracy for fibrosis in patients with non-alcoholic fatty liver disease. Conversely, transient elastography was unreliable for detecting cirrhosis in patients with acute liver damage. The studies are published in the February issue of Hepatology, a journal by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD).
Link between chronic kidney disease and oxygen-deprived tissue
Researchers at the University of Pennsylvania School of Medicine have discovered how low-oxygen conditions can worsen chronic kidney disease (CKD). The key player is a protein called hypoxia-inducible-factor (HIF-1) that, as its name suggests, is active when the kidney does not get enough oxygen, a condition known as hypoxia. The findings appear in a December issue of the Journal of Clinical Investigation.
Protein-dependent 'switch' regulates intracellular trafficking in epithelial cells
With findings highlighted on a recent cover of Developmental Cell, researchers at Weill Cornell Medical College in New York City have shed important new light on key trafficking mechanisms within epithelial cells. Epithelial cells line the outside of nearly all organs.
Researchers find culprit in aging muscles that heal poorly
Communication is critical. Garbled in, garbled out, so to (mis-)speak. Workers who get incomplete instructions produce an incomplete product, and that's exactly what happens with the stem cells in our aging muscles, according to researchers from the Stanford University School of Medicine.
Scientists develop new procedure to differentiate human embryonic stem cells
Molecular scientists at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) – which is part of the University of Texas Health Science Center at Houston – have developed a new procedure for the differentiation of human embryonic stem cells, with which they have created the first transplantable source of lung epithelial cells.
Senescence in liver cells can provoke a beneficial immune reaction
Although post-reproductive life in humans is often associated with decline and a loss of powers, an analogous state in certain cells -- called senescence -- is proving to be one of ironic potency. Scientists at Cold Spring Harbor Laboratory (CSHL) today reported that a particular class of senescent liver cells orchestrates a sequence of events in living mice that can limit fibrosis, a natural response of the liver to acute damage.
To protect against liver disease, body puts cells 'under arrest'
A stable form of cell-cycle arrest known to offer potent protection against cancer also limits liver fibrosis, a condition characterized by an excess of fibrous tissue, according to a new report in the August 22nd Cell, a Cell Press publication. Triggered by chronic liver damage produced by hepatitis infection, alcohol abuse, or fatty liver disease, liver fibrosis can lead to cirrhosis, a major health problem worldwide and the 12th most common cause of death in the United States.

Serum fibrosis markers correlate with liver fibrosis stage in patients with advanced chronic hep C

Related stories:

News discussion: