Washington: Patients suffering from cirrhosis preceded by nonalcoholic steatohepatitis (NASH) are at an equal risk of developing hepatocellular carcinoma (HCC) than those who develop cirrhosis resulting from hepatitis C virus (HCV), a new study by researchers at the Cleveland Clinic has found. The research team, led by Nizar N. Zein, evaluated a total of 510 patients, 315 with liver cirrhosis secondary to chronic HCV infection and 195 with NASH-induced cirrhosis, to compare the incidence of NASH-cirrhosis to HCV-cirrhosis, and to identify HCC risk factors in each group.
The study established that NASH-induced cirrhosis is a much greater risk factor for HCC than previously thought. A related study offers an explanation as to why NASH often progresses to liver cancer. Researchers at Duke University hypothesized that natural killer T (NKT) cells modulate the liver’s response to damage related to fat deposition. NKT cells are specialized types of T lymphoctyes (white blood cells) that reside in healthy livers and regulate immune responses that control tissue inflammation, fibrosis, and cancer progression. Earlier studies from the Duke group and other researchers have demonstrated that the livers of animals and humans with mild forms of nonalcoholic fatty liver disease (NAFLD) were relatively depleted of NKT cells and Th1 cytokines were abundant. In the current study, Anna Mae Diehl and colleagues examined the possibility that excessive accumulation of NKT cells in the liver would tip the cytokine balance in the opposite direction, resulting in liver fibrosis. Results showed that the Hedgehog (Hh) pathway became activated and NKT cells accumulated excessively in the livers of wild type mice that developed NASH-related liver fibrosis. "Hh pathway activation leads to hepatic enrichment with NKT cells that contribute to fibrosis progression in NASH. Our study proves that activation of liver NKT cells generates soluble factors that promote fibrogenesis via a mechanism involving myofibroblastic activation of hepatic stellate cells. Because these results identify novel immune-mediated mechanisms that contribute to fibrosis progression in NASH, the findings have potential clinical implications for one of the most common types of chronic liver injury," Diehl said. The results of the study appear in the June issue of Hepatology. ANI