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However, a sizeable proportion of patients may never progress to cirrhosis. In patients with minimal or no elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and milder degrees of necroinflammation, it was difficult to show any progression during the average of 4 years of follow-up. Similar findings have recently been reported in longitudinal studies of patients with normal serum ALT levels [16]. These results reinforce the recommendation that patients with mild disease activity and scant hepatic fibrosis can delay therapy for hepatitis C until therapeutics improve and regimens are available that are more effective and have fewer side effects [2]. The rate of fibrosis progression is higher among older patients, those with higher serum ALT and AST levels, and those with the most extensive periportal necrosis on initial liver biopsy. For untreated chronic HCV patients, the rates of fibrosis progression was estimated to be in the range of 0.297 and 0.231 fibrosis units per year, as assessed for a group of 70 patients with 170 liver biopsies and a group of 58 control patients used in randomized trials with 116 biopsies [17]. In the study of Ghany et al. (123 chronic HCV pts), the rate of fibrosis progression was found to be much lower (about 0.12 fibrosis units per year), [2]. A striking finding in this study was the lack of correlation between results of cross-sectional and longitudinal analyses. Cross-sectional analysis based on the initial liver biopsy and historical estimates of disease duration yielded a 4-fold higher rate of fibrosis progression than did longitudinal data based on changes between biopsies. This discrepancy was probably due to the inaccuracy in determining the time of onset of infection, which is needed to calculate rate of progression and, perhaps more importantly, the lack of linearity in fibrosis progression. Thus, fibrosis may progress nonlinearly in fits and starts, progressing more rapidly at specific times, perhaps during flares of disease. In addition, progression of fibrosis may not be linear in the same manner as the scoring system, in that progression from stage 0 to 1 may take longer than from stage 3 or 4 or vice versa [2, 18-21].