The distribution of cell cycle phase markers in the first cohort and controls.

<p>Examples of the immunohistochemical staining of Mcm-2, cyclin A, PH3 and p21 in regenerating liver (positive control tissue), liver from a representative patient with ALD and normal liver (negative control tissue). Hepatocyte Mcm-2 expression was higher in ALD and regenerating liver (positive control) compared to normal liver (negative control). Cyclin A and PH3 expression were lower in ALD compared to regenerating liver. In contrast hepatocyte p21 expression was higher in ALD compared to regenerating liver.</p

Hepatocyte p21 expression, MELD score and alcohol consumption at the time of liver biopsy in relation to an adverse liver-related outcome.

<div><p>Kaplan-Meier analysis in 42 patients in the first cohort, divided according to hepatocyte p21 expression above the median [red line] or below the median [black line]) from the time of liver biopsy to outcome or censor point by log-rank test (p=0.03) [4a].</p> <p>Kaplan-Meier analysis of 77 patients in the second cohort from the time of liver biopsy to outcome or censor point by log-rank test - divided according to p21 expression above the median [red line] or below the median [black line] (p<0.0001) [4b]; MELD score above the median [red line] or MELD score below the median [black line] (p=0.03) [4c]; alcohol consumption above the median [red line] or alcohol consumption below the median [black line] (p=0.03) [4d].</p></div

Hepatocyte p21 expression in relation to fibrosis stage and laboratory indices.

<div><p>Hepatocyte p21 expression demonstrated an association with fibrosis stage [2a] in the first cohort; the proportion of hepatocytes that expressed p21 increased with increasing fibrosis stage.</p> <p>Areas of increased α-SMA expression (a marker of activated hepatic stellate cells) were associated with higher hepatocyte p21 expression (2b) than those areas with less α-SMA expression, which were associated with lower hepatocyte p21 expression (2c) even within the same tissue.</p> <p>Expression of hepatocyte p21 correlated positively with prothrombin time in both cohorts (Figure 2d & 2e, respectively) and correlated negatively with serum albumin in the second cohort (Figure 2f).</p></div

Differential hepatocyte p21 expression in the second cohort.

<p>Figure 3 shows fibrosis using reticulin staining (above) and hepatocyte p21 expression (below) in a patient with ALD cirrhosis in second cohort.</p