icon star paper   Articles  
Back grey_arrow_rt.gif
How Often Should Biopsy Be Performed?
  "Rate of natural disease progression in patients with chronic hepatitis C"
Journal of Hepatology, Vol. 38 (3) (2003) pp. 307-314. Jean-Pierre Zarski et al. Dˇpartement d'Hˇpato-gastroentˇrologie, CHU de Grenoble, Grenoble Cedex, France
The interval at which liver biopsy should be repeated in untreated patients with chronic hepatitis C is not defined. We examined fibrosis change by METAVIR scoring in these patients in whom two or more liver biopsies were available. One hundred and eighty patients with histologically proven chronic hepatitis C were studied. Mean delay between biopsies was 3.67±2.69 years and 3.08±1.43 in the 16 patients having three biopsies. Univariate and multivariate analyses were performed to determine factors associated with liver fibrosis progression. Median rate of fibrosis progression per year was 0.04 (0.00-0.55) to first biopsy, 0.00 (0.84-1.02) between first and second biopsy (NS), and 0.17 (0.00-1.50) between second and third biopsy (P<0.05). In multivariate analysis, only age at first biopsy >40 years (OR=5) (2-12) and alcohol consumption of 1-50 g per day (OR=4) (2-12) and more than 50 g per day (OR=8) (3-23) were associated with severe fibrosis. The number of patients who increased in fibrosis stage was significantly higher after 4 years (P<0.02). Conclusions: An interval of at least 4-5 years is needed between liver biopsies to measure change in patients with mild liver disease.
To our knowledge, our current study is the largest study to examine fibrosis progression in which two or more liver biopsies were available in the absence of therapy. At the second biopsy approximately one-third of patients had an increase in fibrosis stage, the majority of them by one unit.
Curiously 14.4% decreased in fibrosis stage. This improvement was also recently found in other studies and in control groups of therapeutic trials. This improvement could be due to sampling error, lack of reproducibility of histological scores, or a true `resolution' of liver fibrosis due to a reduction of co-morbidity factors (obesity, diabetes). However, these factors were not studied, except for alcohol consumption which did not change between the two biopsies.
We found that the median rate of fibrosis progression was shorter between second and third liver biopsies than between first and second liver biopsies. In fact the median duration for an increase of one fibrosis unit was progressively greater with time, confirming that fibrosis progression may not be linear but that there is a progressive acceleration in the latter stages.
Our results show that alcohol even at low levels is a risk factor of fibrosis progression, although alcohol consumption was estimated from retrospective chart review rather than by prospective interview, and as such, measurement of alcohol consumption may be inaccurate. Our results suggest that the reduction of or abstinence from alcohol consumption is one of the few life-style changes that patients can make in order to slow or prevent disease progression.
In univariate analysis the number of patients who achieved an increase in fibrosis was significantly higher when the delay between the two biopsies was longer than 4 years. `Consensus Conferences' have proposed that the delay between two biopsies, especially in patients having a mild liver disease, could be between 3 and 5 years. Our study suggests that the delay could be at least 4-5 years in order to clearly detect a change in the stage of fibrosis in patients with a mild liver disease and without the factor of co-morbidity.
In conclusion, fibrosis progression is very slow in patients with mild chronic hepatitis C, but it does appear to be accelerated in the later stages of disease. Increasing age and daily alcohol consumption are the main factors associated with significant fibrosis. In untreated patients, who do not have risk factors for disease progression, the delay between two biopsies should be at least 4-5 years in order to detect fibrosis progression. However, given the apparent acceleration in fibrosis change in patients with more advanced liver disease, patients with stage 2 or 3 disease should be monitored very closely.
  icon paper stack View Older Articles   Back to Top   www.natap.org