Transient elastography in the early prediction of progressive recurrent hepatitis C following liver transplantation
Authors: Cristina Rigamonti, Maria Francesca Donato, Massimo Colombo
Journal: Hepatology (2010)

Early recognition of recipients with rapidly evolving recurrent hepatitis C following orthotopic liver transplantation (OLT) is the only practical approach to improve outcome of these patients.1 Recently, transient elastography (TE) was shown to identify patients with rapidly progressive hepatitis C in the first year following OLT, differentiating them from patients with slowly progressive hepatitis C.2 Thirty-seven consecutive liver graft recipients with recurrent hepatitis C, who underwent transplantation from June 2005 to December 2007, were prospectively investigated with repeated TE examinations at 3, 6, 9, and 12 months after OLT and underwent a liver biopsy at month 12. Significant liver fibrosis was scored as Ishak staging (S) ≥ 3. Patients with S < 3 at month 12 were defined slow fibrosers compared to rapid fibrosers, who had S ≥ 3. Of the 33 patients who completed the follow-up (four died within month 6), 21 (64%) were slow fibrosers and 12 (36%) were rapid fibrosers, thus confirming the 63% and 37% rates of slow and rapid fibrosers previously reported.2 Slow fibrosers had significantly lower TE measurements at 3, 6, 9, and 12 months (median 7.5, 7.0, 6.9, and 6.4 kPa) compared to rapid fibrosers (median 8.9, 10.9, 11.8, and 13.0 kPa). The 12-month staging was significantly correlated with TE values at month 6 (rho = 0.48, P = 0.006), at month 9 (rho = 0.78, P < 0.0001), and at month 12 (rho = 0.83, P < 0.0001). Rapid fibrosers had significantly higher aspartate aminotransferase serum levels at 3, 6, 9, 12 months, γ-glutamyl transferase serum levels at 6 and 12 months, bilirubin at 6 months, and TE values at 6, 9, and 12 months compared to slow fibrosers. Moreover, rapid fibrosers were more often recipients of aged grafts compared to slow fibrosers, further confirming the prognostic relevance of donor age in this setting of patients. In results from a longitudinal mixed model for repeated measurements, the slope of TE variations was significantly greater in rapid fibrosers (0.40 kPa/month) than in slow fibrosers (−0.05 kPa/month) (P < 0.0001; Fig. 1), further confirming the results of the study by Carrion et al. (0.42 and 0.05 kPa/month in rapid and slow fibrosers, respectively).2 The rates of patients with TE > 7.9 kPa, the optimal TE cut-off for S ≥ 3 diagnosis previously identified by us,3 at 3, 6, 9, and 12 months were 29%, 26%, 31%, and 28% in slow fibrosers and 60%, 67%, 100%, and 95% in rapid fibrosers (P = 0.22, P = 0.06, P = 0.001, and P = 0.001, respectively). By logistic regression analysis, TE > 7.9 kPa at month 6 was the only independent predictor of significant fibrosis at month 12 (P = 0.02, odds ratio = 6.0, 95% confidence interval = 1.2-28.8). The course of liver stiffness assessed by transient elastography during the first year following liver transplantation in slow and rapid fibrosers with recurrent hepatitis C, by a longitudinal mixed model for repeated measurements. By applying in our cohort the bilirubin plus TE model constructed by Carrion et al.2 for identifying rapid fibrosers at month 6, we could correctly classify 67% of our rapid fibrosers, compared to 70% of rapid fibrosers identified by Carrion et al. Interestingly, the 7.9 kPa TE cut-off at month 6 could identify the same proportion (67%) of rapid fibrosers in our cohort. In conclusion, in an external validation group of liver graft recipients with recurrent hepatitis C, repeated TE examinations early after OLT helped to identify patients at risk of progressive graft disease, with a potential benefit for clinical management. Cristina Rigamonti*, Maria Francesca Donato*, Massimo Colombo*, * First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.