Soluble adhesion molecules correlate with liver inflammation and fibrosis in chronic hepatitis C treated with interferon‐α

Abstract

Background: In chronic hepatitis C the relation of circulating adhesion molecules to disease features before, during and after therapy has not been completely established. Aim: To analyse the basal levels of circulating adhesins and the changes induced by interferon in these patients. Methods: We studied, using ELISA assays, the serum levels of soluble intercellular adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1) in 52 patients with chronic hepatitis C on entry, prior to finalizing a 6‐month course of interferon‐α therapy and at the end of the follow‐up. Correlations with clinical, virological and histological features, including inflammation and fibrosis, were calculated by Pearson’s r‐test. Results: Liver necroinflammation was more closely related to sICAM‐1 (r = 0.54, P = 0.0000) than to sVCAM‐1 (r = 0.32, P = 0.02). Fibrosis, both as serum pIIIP and histological scoring, was, however, clearly related to sVCAM‐1 (1071 ± 291 in patients who scored 0–2 vs. 1870 ± 458 in patients who scored 3–4; P = 0.0000). Severe fibrosis was never found below a sVCAM‐1 cut‐off threshold of 1300 ng/mL. Levels of both adhesins did not correlate with viraemia and were comparable among 1b and non‐1b genotypes. Sustained response to interferon was significantly related to low viraemia (P = 0.03), non‐1b type (P = 0.04) and low sICAM‐1 (P = 0.04), but not to sVCAM‐1. On finalizing therapy, patients with normal transaminases had reduced sICAM‐1 (P = 0.0005), but not sVCAM‐1 levels. Conclusions: In chronic hepatitis C, sICAM‐1 was a marker of liver necroinflammation while sVCAM‐1 reflected fibrosis. Both low sVCAM‐1 and pIIIP serum concentrations were strictly linked, suggesting that measuring sVCAM‐1 could give information on the degree of liver fibroplasia.

Adhesive molecules and inflammatory markers among hepatitis C virus Saudi patients

“…Then, our findings appear in agreement with literature data and suggest that VCAM-1, which is considered to reflect the degree of liver fibrosis (25,28) and ICAM-1 levels, markers of liver inflammation, have significantly decreased in HCV patients with normal ALT levels following interferon administration (28,42,46,47). However, the relationship between ICAM-1, VCAM-1 and ALT values does not implicate a direct involvement of these adhesion molecules in physiopathology of hepatocellular damage, but it could only reflect the activation of undergoing immunological mechanisms.…”

“…While, elevated serum VCAM-1 in chronic hepatitis have been reported by some authors (39,40). Also, many authors confirmed our data related to higher levels of sICAM-1 among patients with chronic HCV-related hepatitis than do control subjects (28,41,42). Moreover, similar results are reported in patients with CLD (34) and CHC (18,25).…”

“…The search for alternative non-invasive methods is mandatory especially in follow-up after initial assessment by biopsy (26). Some authors reported that circulating levels of adhesive molecules are related to degree of inflammatory activity and to histological score, suggesting a putative role in monitoring the follow-up (27,28). Others have declared that their measurement adds little to the information provided by traditional biochemistry (29).…”

Role of liver biopsy in management of chronic hepatitis C: A systematic review

“…24 In the study with standard interferon and amantidine28 and the studies of interferon and r i b a~i r i n ,~~~~' pretreatment biopsy findings did not predict virological response to treatment.…”

Intrasplenic transplantation of IL-18 gene-modified hepatocytes: an effective approach to reverse hepatic fibrosis in schistosomiasis through induction of dominant Th1 response

“…7,8 It has been shown in experimental animal models that IFN-␥ is an important therapeutic drug in the treatment of hepatic fibrosis by inhibiting the synthesis of type I and III collagens and decreasing the size of granuloma. [9][10][11][12] In our previous work, 9 we showed that in vivo gene transfer of IFN-␥ in mice with schistosomiasis could significantly decrease the synthesis of type I and III collagens, the expression of TGF-␤1 and its receptor TGF-␤RII in the liver. Because interleukin-18 (IL-18) was initially identified as a strong inducer of IFN-␥ production in mice treated with Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS) 13 and is an important Th1 cytokine, 14 we wondered if delivery of IL-18 gene could play a therapeutic role in the treatment of hepatic fibrosis.…”