We read with great interest the article by Ryder and the Trent Hepatitis C Study Group (Gut 2004;53:451–5) addressing the issue of fibrosis progression in untreated patients with chronic hepatitis C. After examining a large series of paired liver biopsies (median inter-biopsy interval 2.5 years), the authors concluded that even in patients with a “histologically mild” presentation, chronic hepatitis C is characterised by progressive fibrosis. Histological assessment of liver fibrosis in chronic liver diseases is an area of interest to us and we wish to raise a methodological issue concerning Ryder’s study.

While many attempts have been made to standardise non-invasive tests for predicting liver fibrosis, biopsy sampling is currently considered the standard reference for grading and staging chronic hepatitis. Biopsy sampling error and sample size have proved the major sources of bias in liver fibrosis assessment and both variables should be taken into account when the outcome of histology …