Disease- and cell-specific expression of GP73 in human liver disease.

OBJECTIVES: GP73, a Golgi membrane protein, is expressed at high levels in hepatocytes of patients with decompensated cirrhosis. Its expression in other forms of liver disease has not been investigated. Therefore, we studied GP73 expression in patients with noncirrhotic liver disease. METHODS: GP73 expression was detected immunohistochemically and by immunofluorescence microscopy in patients with acute hepatitis of various etiologies, autoimmune hepatitis, chronic HCV infection, and alcoholic liver disease. In order to quantitate hepatocyte GP73 expression, an immunohistochemical scoring system was developed, and validated by a direct comparison with GP73 protein levels as determined by Western blotting. RESULTS: GP73 immunostaining and Western blotting data were highly correlated, demonstrating the suitability of the immunohistochemical scoring system to quantitate hepatocyte GP73 expression. Hepatocyte GP73 expression was increased in patients with acute and autoimmune hepatitis. Treatment of autoimmune hepatitis was associated with a normalization of GP73 expression, indicating that the initial upregulation was reversible. Increased levels of GP73 expression were also noted in chronic HCV infection and alcoholic liver disease. Under these conditions, GP73 levels were correlated with disease stage but not grade. GP73 immunoreactivity was occasionally detected in alpha-SMA-positive, sinusoidal lining cells, suggesting activated stellate cells as a potential source of GP73. CONCLUSIONS: Hepatocyte GP73 levels are upregulated in acute hepatitis and during the progression of liver disease to cirrhosis. This expression pattern suggests the presence of two regulatory mechanisms, the first triggered during acute hepatocellular injury, the second during the progression of chronic liver disease.

Acute pancreatitis in children.

OBJECTIVES: Currently, there is no scoring system for predicting severity in acute pancreatitis in children. Our intent was to evaluate the performance of existing scoring systems in children, to develop a system for children, and to examine the etiology of acute pancreatitis in children. METHODS: A chart review of children with acute pancreatitis was conducted at six centers, three serving as criterion centers and three as validation centers. Ranson and Glasgow scores were calculated for each admission. Additional clinical data were collected, and parameters correlating with severity were incorporated into a new scoring system. Performance characteristics were calculated for each system. RESULTS: A total of 301 admissions were reviewed, 202 in the criterion group and 99 in the validation group. Eight parameters were included in a new scoring system for children. The parameters were as follows: age (<7 yr), weight (<23 kg), admission WBC (>18,500), admission LDH (>2,000), 48-h trough Ca2+ (<8.3 mg/dl), 48-h trough albumin (<2.6 g/dl), 48-h fluid sequestration (>75 ml/ kg/48 h), and 48-h rise in BUN (>5 mg/dl). When the cut-off for predicting a severe outcome was set at 3 criteria, the new system had better sensitivity versus Ranson and Glasgow scores (70% vs 30% and 35%, respectively) and a better negative predictive value (91% vs 85% and 85%). The specificity (79% vs 94% and 94%) and positive predictive value (45% vs 57% and 61%) fell slightly. CONCLUSION: The new scoring system performs better in this group than do existing systems.