HCV-related fibrosis progression following liver transplantation: increase in recent years

doi:10.1016/S0168-8278(00)80231-7

Journal of Hepatology

Volume 32, Issue 4, April 2000, Pages 673-684

https://doi.org/10.1016/S0168-8278(00)80231-7 Get rights and content

Abstract

Background/Aims: The natural history and predictors of HCV-related disease severity post-transplantation are uncertain. The aims of this study were to define the natural history of post-transplantation HCV infection by assessing the rate of fibrosis progression, to determine if the post-transplantation natural history differs from that observed pre-transplantation, and to identify predictors of post-transplantation disease progression.

Methods: Post-transplantation biopsies (mean: 3±1.6/patient) from 284 patients were scored according to histologic stage, using the method of Desmet et al. Change in fibrosis score (fibrosis progression/year) post-transplantation was used as the primary outcome. Predictors analyzed included viral factors (genotype and viral load at transplantation), patient demographics, year of transplantation, country of transplantation, pre-transplantation fibrosis progression, immunosuppression and laboratory data.

Results: There was a linear association between change in fibrosis score and time from transplantation, with a median rate of fibrosis progression per year of 0.3 (0.004–2.19/year). Using parametric time-to-event analysis, the expected median duration to cirrhosis was 10 years. The rate of post-transplantation fibrosis progression was significantly higher than pre-transplantation (0.2/year (0.09–0.8) p<0.0001), and higher in Spanish than US centers (0.48 (0.01–2.19) vs 0.28 (0.004–2.08); p=0.09) despite similar progression rates prior to transplantation. Variables independently associated with post-transplantation progression included year of transplantation (p=0.0001), race (p=0.02), number of methyl-prednisolone boluses (p=0.03), and HCV RNA levels at transplantation (p=0.01).

Conclusions: HCV-related disease progression is accelerated in immunocompromised compared to immunocompetent patients, with a progressive increase in patients who have recently undergone liver transplantation. Changes in patient management post-transplantation over time and between transplant centers may account for the increase in fibrosis progression observed in recent years.

Section snippets

Study population

Two hundred and eighty-four patients with HCV infection following liver transplantation formed the study group. Of these, 203 were patients who had undergone transplantation at the University of California, San Francisco, USA between June 1988 and December 1996, whereas the remaining 81 patients had undergone transplantation at the Hospital Universitario La FE in Valencia, Spain, between March 1991 and May 1996. Patient features and outcomes were representative of other centers in their

Patient outcome in Spanish and US patients

Patient survival was similar in Spanish and US centers, with a 5-year survival rate of 84% and 81%, respectively. The HCV-related mortality rate was also similar in both centers, representing approximately half of the deaths in both countries (5/11 vs 21/41, respectively). HCV-related deaths were very similar to those from non-HCV causes. At 3 years post-transplantation the rates were 6.2% and 7.7%, respectively. At 5 years post-transplantation, the rates were 9.0% and 9.7%, respectively. The

Discussion

HCV is an important indication for liver transplantation in all transplant centers in both the USA and Europe 1., 2.. Unfortunately, recurrence of HCV infection is almost universal in patients with pre-transplantation viremia (3), and development of HCV-related disease occurs in at least 50% of patients after 1 year (4). Knowledge of the natural history of HCV infection following liver transplantation is essential for making rational decisions about liver transplant indications or early

Acknowledgements

Grant support was received from“Asociación Española para el Estudio del Hígado” (M.B.), NIDDK Liver Center DK26743 (M.B., L.F., N.A., T.L.W), NIAID AI40034 (T.L.W, M.K.).