The Natural History of Liver Fibrosis Progression Rate in Hepatitis C Infection (DDW 4/26/10)

[object Object],[object Object],[object Object],Background Summary Factors that determine the rate of progression of liver fibrosis in hepatitis C virus infection (HCV) are difficult to identify given the indolent and chronic nature of HCV. We previously reported the association between multiple co-morbid illnesses, as well as other variables, and liver fibrosis score from a single biopsy. Objectives This study was designed to assess liver fibrosis rate in a patient population with HCV infection and identify variables associated with accelerated fibrosis in these patients. Methods Results ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],References Conclusions Change in fibrosis score between liver biopsies was variable. One-third of our population progressed over a mean interval of ~4 years between biopsies, but there were no variables that clearly correlated with fibrosis progression. Given the progression rates, it is reasonable to stage fibrosis every 3-5 years even in those without the known factors that accelerate fibrosis progression. The best modality for staging remains liver biopsy, but serial non-invasive tests should be studied to determine if they can supplant biopsy. Study Limitations The major limitation of this study was the low frequency of patients with multiple biopsies. Although the cohort was rather sizeable (n=800), only 72 of these patients had >1 liver biopsy. This significantly reduced the statistical power of the study. Furthermore, due to the retrospective study design and the large number of variables evaluated, certain variable values were not available for a number of patients. This also may have weakened the strength of some statistical comparisons. A high rate of liver biopsy sampling error in patients with diffuse parenchymal liver disease—even in two biopsies taken simultaneously—may also have made the assessment of serial biopsies more difficult. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],The mean interval between biopsies was 4.2±3.1 (range 0.1-19.0) years and the overall liver fibrosis progression rate was 0.17±0.52 MFP/year. Twelve patients (16.7%) had lower fibrosis stage on subsequent biopsy, 34 patients (47.2%) had no change and 26 patients (36.1%) had increased fibrosis stage on subsequent biopsy. Results Primary Characteristics Seventy-two patients (46 male; 26 female) with >1 liver biopsy were identified . The ethnic distribution was 50% white, 8% African American, 1.4% Asian, 4% Hispanic and 36% other/unknown. Mean age at HCV acquisition was 20.1 ±7.0 (range 0-39) years. Mean age at first biopsy was 48.0 ±7.7 (range 33-70) and at second biopsy was 50.9±7.7 (range 35-70). Gender Ethnicity Age Overall Fibrosis Progression Twenty six patients (36.1%) failed IFN therapy prior to the first liver biopsy, with a liver fibrosis progression rate of 0.14 ±0.63 MFP/year. Amongst the 46 patients (63.9%) who did not receive IFN therapy, the overall liver fibrosis progression rate was higher at 0.19 ± 0.45 MFP/year. The difference in liver fibrosis progression rates between the IFN-treated group and non-IFN-treated group was not significant (p=0.60). Results Antiviral Therapy There were no significant associations appreciated between fibrosis progression rate and other variables evaluated including age at time of HCV acquisition or first biopsy, alcohol use, smoking, risk factors for HCV transmission, diabetes, and other laboratory values. We could not identify an age “cut-off” that could predict increased risk for accelerated fibrosis progression. Human Immunodeficiency Virus Status Other Variables Patient Demographics Seeff LB. Natural history of hepatitis C. Hepatology 1997 26(3 Suppl 1); 21s-28s. Poynard T, et al . Rates and risk factors for liver fibrosis progression in patients with chronic hepatitis c. J Hepatol. 2001;34(5):730-739. Ghany MG, et al . Progression of fibrosis in chronic hepatitis C. Gastroenterology 2003;124:97-104. Schiff ER, et al . Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection . Am J Gastroenterol. 2002;97:2614-2618.

The Natural History of Liver Fibrosis Progression Rate in Hepatitis C Infection (DDW 4/26/10)

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