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575 Oninvasive prediction of fibrosis by a novel serum marker in patients with chronic hepatitis C
438A
AASLD ABSTRACTS
HEPATOLOGY, October 2003
575
576
ONINVASIVE PREDICTION OF FIBROSIS BY A NOVEL SERUM MARKER IN PATIENTS WITH CHRONIC HEPATITIS C. Yukiko Saitou, Katsuya Shiraki, Tomoyuki Kawakita,
LIVER ELASTICITY MEASUREMENT BY ULTRASONIC TRANSIENT ELASTOGRAPHY: A NEW NON-INVASIVE METHOD FOR ASSESSMENT OF LIVER FIBROSIS IN CHRONIC VIRAL HEPATITIS. Michel Beaugrand, Marianne Ziol,
Hidekazu Inoue, Hiroshi Okano, Norihiko Yamamoto, Kazushi Sugimoto, Kazumoto Muraki, Takeshi Nakano, First Internal Medicine, Mie University, Tsu, Japan Background: YKL-40 (also known as h u m a n cartilage protein 39 and a growth factor of connective tissue cells and of endothelial cells) is a mammalian m e m b e r of the chitinase protein family. Although the function of YKL-40 is not well known yet, the pattern of its expression suggests it may play a certain role in remodeling or degradation of extracellular matrix. Some previous studies showed YKL-40 may reflect liver fibrosis in alcoholic liver disease. However, its meaning in HCV related liver disease has not b e e n well studied. Therefore, we investigated the correlation between the serum fibrosis makers including YKL-40 and the staging of liver fibrosis in chronic hepatitis C, between the markers and the grading of liver activity. And furthermore we investigated the changes of serum markers to the outcome of the interferon (IFN) treatment and compared there utility to the effect of IFN treatment at the side of the virology. Materials and Methods: We selected the N-terminal propeptide of type IIIprocollagen(PIIIP), typeIVcollagen, hyaluronic acid(HA) and YKL-40 to serum fibrosis markers. These fibrosis markers were assayed in 100 patients with chronic hepatitis C. Serum PIIIP and typeWcollagen values were assessed by radioimmunoassay, HA and YKL-40 values were assayed using sandwich enzyme immunoassay. The relationships between each parameter's value and histological fibrosis score (F0-4), activity score(A0-3) were studied before IFN treatment. And the changes of each values were compared before and 6 months after IFN treatment in 63 patients with chronic hepatitis C.Results: There was a good correlation between each parameter's value and the histological fibrosis score before IFN treatment(ANOVA, p<0.0001). Particularly, HA could discriminate F4 from F1-3(p<0.0001), while YKL-40 and PIIIP demonstrated the strong classification between F0-1 and F2-4(p<0.0001). As for the histological activity score, the serum markers without YKL-40 had a correlation (ANOVA, p<0.05). After IFN treatment, the patients were classified into non-virological responders (NR), and virological responders (VR). In NR group, each parameter's value except for YKL-40 did not change, but YKL-40 value decreased(p <0.005). W h e n NR group was classified into serological responders (SR) and non-serological responders(NSR), YKL-40 value decreased in the SR group more than NSR group(p-0.017 vs p-0.034). In VR group, each parameter value except for typeIV collagen t e n d e d to decrease after IFN treatment(p<0.01). Conclusion. YKL-40 could be a new sensitive marker for the fibrosis of chronic hepatitis C and for the prediction of the efficiency of IFN treatment. Our study demonstrated that serum fibrosis markers including YKL-40 might highly evaluate the degrees of histological fibrosis without biopsy. Disclosures: Hidekazu Inoue - No relationships to disclose Tomoyuki Kawakita - No relationships to disclose Kazumoto Muraki - No relationships to disclose Takeshi Nakano - No relationships to disclose Hiroshi Okano - No relationships to disclose Yukiko Saitou - No relationships to disclose Katsuya Shiraki - No relationships to disclose Kazushi Sugimoto - No relationships to disclose Norihiko Yamamoto - No relationships to disclose
CHU Jean Verdier, Bondy, France; Laurenf Sandrin, Cdline Fournier, chosens, Paris, France;Annonciade Biaggi-Frassati, Bruno Poulet, Jean-Claude Trinchet, CHU Jean Verdier, Bondy, France; Frdd~'c Mal, Christos Christ~'dis, Instffut Mutualiste Montsouris, Paris, France; Farhad Kazemi, V&onique Grando, Nathalie Ganne, CHU Jean Verdier, Bondy, France; Robert Palau, Institut Mutualiste Montsouris, Paris, France Despite limitations, histologic evaluation of liver biopsy remains the gold standard for assessing fibrosis. Recently, the need for non-invasive methods has been advocated. Firmness of the liver is the hallmark of liver fibrosis but up to now no method was available for a simple and reliable measurement of liver elasticity. A new non-invasive device has been developed to measure liver stiffness. Its probe consists in an ultrasonic transducer mounted on the axis of a low frequency vibrator. The latter generates an elastic wave whose propagation velocity is directly related to the medium elasticity. This velocity is estimated from the ultrasonic signals acquired during the elastic wave propagation. On each patient, several measurements (mean 10) were performed by intercostal route on the left hepatic lobe (25 and 45 m m below the skin) and a median elasticity value in kPa was obtained. The aim of this study was to assess this new technique on 220 patients with histologically proven HCV (n-202) or HCB (n-18)-related chronic hepatitis and no ascites. All patients had a liver biopsy and a liver elasticity measurement within less than a year (mean delay: 27 days). Two pathologists unaware of the results assessed independently liver fibrosis using the Metavir scoring system and reached consensus score in case of disagreement. In 45 cases, no reliable histological scoring could be made, due to inadequate sample size. In 3 patients, due to overweight, no reliable liver elasticity measurement could be obtained. Within the 172 remaining patients, 6 were F0 (mean elasticity: 5.5 kPa, standard deviation: 1.6 kPa), 47 were F1 (5.7 ± 2.0 kPa), 54 were F2 (9.9 ± 8.4 kPa), 21 were F3 (11.4 ± 5.9 kPa) and 44 were F4 (31.5 ± 18.5 kPa). The Spearman correlation coefficient between liver elasticity and fibrosis score was 0.74 (p < 0.01). Receiver operating characteristic (ROC) analysis was performed (cf. figure) for fibrosis -> F2, -> F3 and F4 and the areas under the ROC curves were 0.86, 0.88 and 0.92, respectively. Transient elastography is a promising simple, non-invasive and reliable method to evaluate hepatic fibrosis in patients with chronic viral hepatitis.
ROecur e
02
0~
0
AASLD ABSTRACTS
HEPATOLOGY, October 2003
575
576
ONINVASIVE PREDICTION OF FIBROSIS BY A NOVEL SERUM MARKER IN PATIENTS WITH CHRONIC HEPATITIS C. Yukiko Saitou, Katsuya Shiraki, Tomoyuki Kawakita,
LIVER ELASTICITY MEASUREMENT BY ULTRASONIC TRANSIENT ELASTOGRAPHY: A NEW NON-INVASIVE METHOD FOR ASSESSMENT OF LIVER FIBROSIS IN CHRONIC VIRAL HEPATITIS. Michel Beaugrand, Marianne Ziol,
Hidekazu Inoue, Hiroshi Okano, Norihiko Yamamoto, Kazushi Sugimoto, Kazumoto Muraki, Takeshi Nakano, First Internal Medicine, Mie University, Tsu, Japan Background: YKL-40 (also known as h u m a n cartilage protein 39 and a growth factor of connective tissue cells and of endothelial cells) is a mammalian m e m b e r of the chitinase protein family. Although the function of YKL-40 is not well known yet, the pattern of its expression suggests it may play a certain role in remodeling or degradation of extracellular matrix. Some previous studies showed YKL-40 may reflect liver fibrosis in alcoholic liver disease. However, its meaning in HCV related liver disease has not b e e n well studied. Therefore, we investigated the correlation between the serum fibrosis makers including YKL-40 and the staging of liver fibrosis in chronic hepatitis C, between the markers and the grading of liver activity. And furthermore we investigated the changes of serum markers to the outcome of the interferon (IFN) treatment and compared there utility to the effect of IFN treatment at the side of the virology. Materials and Methods: We selected the N-terminal propeptide of type IIIprocollagen(PIIIP), typeIVcollagen, hyaluronic acid(HA) and YKL-40 to serum fibrosis markers. These fibrosis markers were assayed in 100 patients with chronic hepatitis C. Serum PIIIP and typeWcollagen values were assessed by radioimmunoassay, HA and YKL-40 values were assayed using sandwich enzyme immunoassay. The relationships between each parameter's value and histological fibrosis score (F0-4), activity score(A0-3) were studied before IFN treatment. And the changes of each values were compared before and 6 months after IFN treatment in 63 patients with chronic hepatitis C.Results: There was a good correlation between each parameter's value and the histological fibrosis score before IFN treatment(ANOVA, p<0.0001). Particularly, HA could discriminate F4 from F1-3(p<0.0001), while YKL-40 and PIIIP demonstrated the strong classification between F0-1 and F2-4(p<0.0001). As for the histological activity score, the serum markers without YKL-40 had a correlation (ANOVA, p<0.05). After IFN treatment, the patients were classified into non-virological responders (NR), and virological responders (VR). In NR group, each parameter's value except for YKL-40 did not change, but YKL-40 value decreased(p <0.005). W h e n NR group was classified into serological responders (SR) and non-serological responders(NSR), YKL-40 value decreased in the SR group more than NSR group(p-0.017 vs p-0.034). In VR group, each parameter value except for typeIV collagen t e n d e d to decrease after IFN treatment(p<0.01). Conclusion. YKL-40 could be a new sensitive marker for the fibrosis of chronic hepatitis C and for the prediction of the efficiency of IFN treatment. Our study demonstrated that serum fibrosis markers including YKL-40 might highly evaluate the degrees of histological fibrosis without biopsy. Disclosures: Hidekazu Inoue - No relationships to disclose Tomoyuki Kawakita - No relationships to disclose Kazumoto Muraki - No relationships to disclose Takeshi Nakano - No relationships to disclose Hiroshi Okano - No relationships to disclose Yukiko Saitou - No relationships to disclose Katsuya Shiraki - No relationships to disclose Kazushi Sugimoto - No relationships to disclose Norihiko Yamamoto - No relationships to disclose
CHU Jean Verdier, Bondy, France; Laurenf Sandrin, Cdline Fournier, chosens, Paris, France;Annonciade Biaggi-Frassati, Bruno Poulet, Jean-Claude Trinchet, CHU Jean Verdier, Bondy, France; Frdd~'c Mal, Christos Christ~'dis, Instffut Mutualiste Montsouris, Paris, France; Farhad Kazemi, V&onique Grando, Nathalie Ganne, CHU Jean Verdier, Bondy, France; Robert Palau, Institut Mutualiste Montsouris, Paris, France Despite limitations, histologic evaluation of liver biopsy remains the gold standard for assessing fibrosis. Recently, the need for non-invasive methods has been advocated. Firmness of the liver is the hallmark of liver fibrosis but up to now no method was available for a simple and reliable measurement of liver elasticity. A new non-invasive device has been developed to measure liver stiffness. Its probe consists in an ultrasonic transducer mounted on the axis of a low frequency vibrator. The latter generates an elastic wave whose propagation velocity is directly related to the medium elasticity. This velocity is estimated from the ultrasonic signals acquired during the elastic wave propagation. On each patient, several measurements (mean 10) were performed by intercostal route on the left hepatic lobe (25 and 45 m m below the skin) and a median elasticity value in kPa was obtained. The aim of this study was to assess this new technique on 220 patients with histologically proven HCV (n-202) or HCB (n-18)-related chronic hepatitis and no ascites. All patients had a liver biopsy and a liver elasticity measurement within less than a year (mean delay: 27 days). Two pathologists unaware of the results assessed independently liver fibrosis using the Metavir scoring system and reached consensus score in case of disagreement. In 45 cases, no reliable histological scoring could be made, due to inadequate sample size. In 3 patients, due to overweight, no reliable liver elasticity measurement could be obtained. Within the 172 remaining patients, 6 were F0 (mean elasticity: 5.5 kPa, standard deviation: 1.6 kPa), 47 were F1 (5.7 ± 2.0 kPa), 54 were F2 (9.9 ± 8.4 kPa), 21 were F3 (11.4 ± 5.9 kPa) and 44 were F4 (31.5 ± 18.5 kPa). The Spearman correlation coefficient between liver elasticity and fibrosis score was 0.74 (p < 0.01). Receiver operating characteristic (ROC) analysis was performed (cf. figure) for fibrosis -> F2, -> F3 and F4 and the areas under the ROC curves were 0.86, 0.88 and 0.92, respectively. Transient elastography is a promising simple, non-invasive and reliable method to evaluate hepatic fibrosis in patients with chronic viral hepatitis.
ROecur e
02
0~
0