Mechanisms and biomarkers of apoptosis in liver disease and fibrosis.

Liver fibrosis and cirrhosis are a major cause of morbidity and mortality worldwide. Development of the fibrotic scar is an outcome of chronic liver diseases of varying aetiologies including alcoholic liver disease (ALD) nonalcoholic liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) viral hepatitis B and C (HBV, HCV). The critical step in the development of scar is activation of hepatic stellate cells (HSCs), which become the primary source of extracellular matrix.

Paediatric cholestatic liver disease: Diagnosis, assessment of disease progression and mechanisms of fibrogenesis.

Cholestatic liver disease causes significant morbidity and mortality in children. The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy. There is no single gold standard test that accurately reflects the presence of liver disease, or that can be used to monitor fibrosis progression, particularly in conditions such as cystic fibrosis.

Importance of hepatic fibrosis in cystic fibrosis and the predictive value of liver biopsy.

Unlabelled: Cystic fibrosis liver disease (CFLD), which results from progressive hepatobiliary fibrosis, is an important cause of morbidity and mortality, but it is difficult to identify before portal hypertension (PHT) ensues. Clinical signs, serum alanine aminotransferase (ALT) levels, and ultrasound (US) are widely applied, but their value in predicting the presence of cirrhosis, the development of PHT, or adverse outcomes is undetermined. The potential gold standard, liver biopsy, is not standard practice and, notwithstanding sampling error considerations, has not been systematically evaluated.

Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis.

The mechanisms for progressive fibrosis and exacerbation by steatosis in patients with chronic hepatitis C (HCV) are still unknown. We hypothesized that proliferative blockade in HCV-infected and steatotic hepatocytes results in the default activation of hepatic progenitor cells (HPC), capable of differentiating into both biliary and hepatocyte lineages, and that the resultant ductular reaction promotes portal fibrosis. To study this concept, 115 liver biopsy specimens from subjects with HCV were scored for steatosis, inflammation, and fibrosis.

Steatosis and liver cell apoptosis in chronic hepatitis C: a mechanism for increased liver injury.

Steatosis is increasingly recognized as a cofactor influencing the progression of fibrosis in chronic hepatitis C; however, the mechanisms by which it contributes to liver injury remain uncertain. We studied 125 patients with chronic hepatitis C to assess the effect of steatosis on liver cell apoptosis and the expression of Bcl-2, Bcl-x(L), Bax, and tumor necrosis factor alpha (TNF-alpha) and the relationship between liver cell apoptosis and disease severity. A significant increase in liver cell apoptosis was seen in liver sections with increasing grade of steatosis (r = 0.