The evaluation of hepatic fibrosis on histological sections is of great interest for the staging and follow-up of chronic liver disease. Because no reliable scoring system is yet available, we have designed a semiquantitative scoring system in which the four main sites of fibrotic deposit--centrilobular vein, portal tract and perisinusoidal space, together with width and number of septa when present--are analyzed. These different items have been previously settled from comparison with morphometric measurements to evaluate surface density of total collagen performed on the same liver needle biopsy specimens stained with picro-sirius. The score has been tested on samples from 200 consecutive patients with various liver diseases and compared with the surface density of total collagen and Knodell scoring system. For observer variation study, the features by three independent pathologists were coded on 20 cases. There was a good interobserver (Kendall's tau-b = 0.75) and intraobserver (tau-B = 0.73) reproducibility. Each component of the fibrosis scoring system and total collagen surface density were significantly linearly related (one-way polynomial analysis, p < 10(-4); the correlation between semiquantitative scoring system and surface density of total collagen was 0.73 (p < 10(-5). Our semiquantitative scoring system, simple and reproducible, describes both liver architecture and fibrotic deposit. It is better related to morphometric measurement of fibrosis than each of its constituents or than the fibrosis item of the Knodell scoring system. It represents a reliable and convenient method for fibrosis evaluation, which is mandatory for clinical use.

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A member of the glutathione S-transferase family, Sm28GST has previously demonstrated a good ability to protect rodents against experimental infection with Schistosoma mansoni. In order to evaluate its efficacy in a model closer to man, two different protocols of immunization with recombinant Sm28GST were tested on baboons in a large-scale trial. Three injections in the presence of aluminium hydroxide as adjuvant resulted in a significant 38% reduction in the adult worm burden together with a trend for a lower percentage of inflammatory tissue in the liver. Individual levels of protection, ranging from 0 to 80%, underlined the heterogeneity of the immune response to this purified molecule in outbred primates. On the other hand, two injections of Sm28GST in the presence of aluminium hydroxide and Bordetella pertussis reduced female schistosome fecundity by 33%, with a more pronounced effect (66%) on faecal egg output; there was also a trend, in this protocol, for decrease of the mean granuloma surface in the liver. Individual anti-Sm28GST IgG antibodies were apparently unrelated to levels of immunity, but there was partial evidence that cytophilic IgE might play a role in the immune mechanisms affecting worm viability, but not fecundity. In the mouse model, Sm28GST vaccination resulted in a lower hatching ability of tissue eggs recovered from immunized mice whereas passive transfer of specific anti-Sm28GST T-lymphocytes, one day before infection, significantly reduced the number of eggs in the liver of mice. We propose that different protocols of immunization with a recombinant molecule can impede Schistosoma mansoni worm viability and fecundity, but can also affect miracidium physiology, with important consequences for disease transmission and granuloma-derived pathology.

The aim of this study was to evaluate the effect of interferon-alpha on liver fibrosis with an established quantitative histochemical method for determining collagen as a marker. 59 patients (31 men, 28 women; 47 +/- 14 yr) with chronic non-A, non-B hepatitis (92% with hepatitis C virus antibody) received subcutaneous injections of 3 or 1 MU recombinant interferon-alpha 2b or placebo thrice weekly for 24 wk. Needle-biopsy sections taken before and after interferon treatment were examined for histological evaluation and collagen quantitation. Values were compared with results obtained by means of morphometrical analysis of liver collagen and Knodell scoring histological index. The index of periportal and/or bridging necrosis was the only component of Knodell's histological score significantly decreased (p < 0.05) in patients treated with 3 MU interferon compared with placebo-treated controls. The fibrosis score was not significantly changed. In contrast, liver total collagen variations measured colorimetrically and morphometrically were significantly decreased in patients treated with 3 MU and 1 MU compared with the increase observed in the placebo-treated controls (p < 0.05). From these results, we conclude that a 6-mo course of 3 MU or 1 MU interferon-alpha 2b causes slight but nonetheless significant regression of liver fibrosis as assessed on the basis of quantitative estimation of liver collagen, irrespective of other response criteria, whereas progression of liver fibrosis can be observed in the absence of treatment.