Longitudinal variation in hepatitis C virus (HCV) viraemia and early course of HCV infection after liver transplantation for HCV cirrhosis: the role of different immunosuppressive regimens

Abstract

Background: The role of the type of immunosuppression in the natural history of post-transplant hepatitis C virus (HCV) infection is unclear.

Aims: To evaluate the fluctuation of HCV viraemia and the early course of infection, and their relation to the type of immunosuppression in HCV transplant patients.

Methods: In 47 HCV transplant patients, serum HCV RNA levels were determined pretransplant and at one and two weeks, and three and 12 months after transplant. Initial immunosuppression was triple (cyclosporin, azathioprine, prednisolone) in 31, double (cyclosporin, prednisolone) in five, and single (cyclosporin or tacrolimus) in 11 patients. Prednisolone was withdrawn at a median of six months.

Results: At three months, HCV RNA levels were higher in patients with single than with triple or double initial therapy. At 12 months, HCV RNA levels correlated only with duration of prednisolone treatment and were relatively higher in patients with triple compared with single initial immunosuppression. A higher necroinflammatory activity at 12 months post-transplant was found in patients with post-transplant acute hepatitis compared with those without. Extent of fibrosis at 12 months was associated with the 12 month HCV RNA level and occurrence of post-transplant acute hepatitis.

Conclusions: HCV RNA levels at three months after transplant are higher in patients treated with single initial immunosuppressive therapy, but at 12 months are higher in patients with longer duration of steroid treatment. HCV viraemia at 12 months seems to be particularly important, as its levels are strongly correlated with the severity of fibrosis.

Figure 1

Serum HCV RNA levels pretransplant and at one week (in 35 patients), two weeks (in 38 patients), and three and 12 months post-transplant in 47 patients transplanted for HCV cirrhosis in relation to the type of initial immunosuppressive therapy. Initial immunosuppressive therapy was triple (cyclosporin, azathioprine, prednisolone) in 31, double (cyclosporin and prednisolone) in five, and single (eight cyclosporin; three tacrolimus) in 11 patients. Box and whisker plots express medians, and interquartile and overall ranges. The outlying values are plotted individually. HCV RNA levels are presented in a logarithmic scale.

Figure 2

Serum HCV RNA levels pretransplant and at one week (in 35 patients), two weeks (in 38 patients), and three and 12 months post-transplant in 47 patients transplanted for HCV cirrhosis in relation to the occurrence of acute hepatitis C. Box and whisker plots express medians, and interquartile and overall ranges. The outlying values are plotted individually. HCV RNA levels are presented in a logarithmic scale.

Figure 3

Serum HCV RNA levels pretransplant and at one week (in 35 patients), two weeks (in 38 patients), and three and 12 months post-transplant in 47 patients transplanted for HCV cirrhosis in relation to chronic hepatitis grading score. Box and whisker plots express medians, and interquartile and overall ranges. The outlying values are plotted individually. HCV RNA levels are presented in a logarithmic scale.

Figure 4

Serum HCV RNA levels pretransplant and at one week (in 35 patients), two weeks (in 38 patients), and three and 12 months post-transplant in 47 patients transplanted for HCV cirrhosis in relation to fibrosis or chronic hepatitis staging score. Box and whisker plots express medians, and interquartile and overall ranges. The outlying values are plotted individually. HCV RNA levels are presented in a logarithmic scale.