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ATLANTA — A blood test can predict nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease, according to results of a study presented at a meeting sponsored by the American Association for the Study of Liver Diseases.
Hepatocyte apoptosis is known to mediate liver injury in nonalcoholic fatty liver disease (NAFLD). The activation of caspases that mediate apoptosis can be measured in the plasma, thus allowing an indirect evaluation of liver damage.
Plasma caspase activation was detected using an enzyme-linked immunosorbent assay for cytokeratin-18 fragments, which are a byproduct of caspase activation. In the study, caspase activation was strongly linked to disease severity; a cutoff value of 395 U/L was 99.9% sensitive and 85.7% specific in predicting nonalcoholic steatohepatitis (NASH).
“A liver biopsy is the only reliable method to differentiate simple steatosis from NASH and stage disease severity,” noted study author Dr. Anna Wieckowska of the Cleveland Clinic. However, biopsy has inherent risks and is not practical to perform multiple times.
Dr. Wieckowska and her associates evaluated a caspase activity blood test in 44 consecutive patients with suspected NAFLD. They measured caspase activity in plasma samples obtained at the time of liver biopsy, and then correlated the blood test results with histopathologic features.
Five patients were excluded because of a hemolyzed blood sample, two were excluded because they had borderline NASH, and two had alternative diagnoses, which left 39 evaluable patients.
Caspase activation was significantly elevated in patients with definitive NASH, with median cytokeratin-18 levels of 767 U/L, compared with 202 U/L in patients with simple steatosis. After adjustment for confounding variables, including aspartate aminotransferase/alanine aminotransferase ratio and body mass index, cytokeratin-18 levels were independently predictive of NASH, with a positive predictive value of 99.9% and a negative predictive value of 85.7%.
“This is potentially a very exciting breakthrough if confirmed in a larger series,” commented Dr. Keith D. Lindor of the Mayo Clinic Foundation in Rochester, Minn. He added that “a noninvasive way to accurately predict mild degrees of fibrosis would allow us to select patients for treatment trials and also perhaps serve as a reliable and clinically relevant end point for these studies.”
ATLANTA — A blood test can predict nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease, according to results of a study presented at a meeting sponsored by the American Association for the Study of Liver Diseases.
Hepatocyte apoptosis is known to mediate liver injury in nonalcoholic fatty liver disease (NAFLD). The activation of caspases that mediate apoptosis can be measured in the plasma, thus allowing an indirect evaluation of liver damage.
Plasma caspase activation was detected using an enzyme-linked immunosorbent assay for cytokeratin-18 fragments, which are a byproduct of caspase activation. In the study, caspase activation was strongly linked to disease severity; a cutoff value of 395 U/L was 99.9% sensitive and 85.7% specific in predicting nonalcoholic steatohepatitis (NASH).
“A liver biopsy is the only reliable method to differentiate simple steatosis from NASH and stage disease severity,” noted study author Dr. Anna Wieckowska of the Cleveland Clinic. However, biopsy has inherent risks and is not practical to perform multiple times.
Dr. Wieckowska and her associates evaluated a caspase activity blood test in 44 consecutive patients with suspected NAFLD. They measured caspase activity in plasma samples obtained at the time of liver biopsy, and then correlated the blood test results with histopathologic features.
Five patients were excluded because of a hemolyzed blood sample, two were excluded because they had borderline NASH, and two had alternative diagnoses, which left 39 evaluable patients.
Caspase activation was significantly elevated in patients with definitive NASH, with median cytokeratin-18 levels of 767 U/L, compared with 202 U/L in patients with simple steatosis. After adjustment for confounding variables, including aspartate aminotransferase/alanine aminotransferase ratio and body mass index, cytokeratin-18 levels were independently predictive of NASH, with a positive predictive value of 99.9% and a negative predictive value of 85.7%.
“This is potentially a very exciting breakthrough if confirmed in a larger series,” commented Dr. Keith D. Lindor of the Mayo Clinic Foundation in Rochester, Minn. He added that “a noninvasive way to accurately predict mild degrees of fibrosis would allow us to select patients for treatment trials and also perhaps serve as a reliable and clinically relevant end point for these studies.”
ATLANTA — A blood test can predict nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease, according to results of a study presented at a meeting sponsored by the American Association for the Study of Liver Diseases.
Hepatocyte apoptosis is known to mediate liver injury in nonalcoholic fatty liver disease (NAFLD). The activation of caspases that mediate apoptosis can be measured in the plasma, thus allowing an indirect evaluation of liver damage.
Plasma caspase activation was detected using an enzyme-linked immunosorbent assay for cytokeratin-18 fragments, which are a byproduct of caspase activation. In the study, caspase activation was strongly linked to disease severity; a cutoff value of 395 U/L was 99.9% sensitive and 85.7% specific in predicting nonalcoholic steatohepatitis (NASH).
“A liver biopsy is the only reliable method to differentiate simple steatosis from NASH and stage disease severity,” noted study author Dr. Anna Wieckowska of the Cleveland Clinic. However, biopsy has inherent risks and is not practical to perform multiple times.
Dr. Wieckowska and her associates evaluated a caspase activity blood test in 44 consecutive patients with suspected NAFLD. They measured caspase activity in plasma samples obtained at the time of liver biopsy, and then correlated the blood test results with histopathologic features.
Five patients were excluded because of a hemolyzed blood sample, two were excluded because they had borderline NASH, and two had alternative diagnoses, which left 39 evaluable patients.
Caspase activation was significantly elevated in patients with definitive NASH, with median cytokeratin-18 levels of 767 U/L, compared with 202 U/L in patients with simple steatosis. After adjustment for confounding variables, including aspartate aminotransferase/alanine aminotransferase ratio and body mass index, cytokeratin-18 levels were independently predictive of NASH, with a positive predictive value of 99.9% and a negative predictive value of 85.7%.
“This is potentially a very exciting breakthrough if confirmed in a larger series,” commented Dr. Keith D. Lindor of the Mayo Clinic Foundation in Rochester, Minn. He added that “a noninvasive way to accurately predict mild degrees of fibrosis would allow us to select patients for treatment trials and also perhaps serve as a reliable and clinically relevant end point for these studies.”