Influence of steroids on HCV recurrence after liver transplantation: A prospective study

doi:10.1016/j.jhep.2007.07.023

Journal of Hepatology

Volume 47, Issue 6, December 2007, Pages 793-798

https://doi.org/10.1016/j.jhep.2007.07.023 Get rights and content

Background/Aims

To assess the effect of long-term maintenance of steroids on HCV recurrence after liver transplantation (LT), that is still controversial, a prospective multicentre trial was conducted at the centres of Bologna and Padua, Italy.

Methods

From September 2002, 47 eligible HCV positive LT recipients were randomized to receive 2 different steroid schedules in association with tacrolimus: group A: rapid tapering and withdrawal 91 days after LT group B: slow tapering and withdrawal 25 months after LT. Thirty-nine patients were assessable: 23 in group A and 16 in group B. Donor and recipient characteristics were similar in the two groups. Median follow-up was 841 days (130–1376). One hundred liver biopsies were performed, and every patient had a biopsy at month 12.

Results

Twenty-two out of 23 (95, 65%) patients in group A and 15 out of 16 (93, 75%) in group B had histologically-confirmed HCV recurrence. Twelve-month histology showed advanced fibrosis (score 3 or 4) in 42.1% of the patients in group A versus 7.6% in group B (P = 0.03). One-and 2-year advanced fibrosis-free survival were 65.2 and 60.8 in group A and 93.7% in group B (P = 0.03 and = 0.02, respectively).

Conclusions

Slow tapering of steroids reduced the progression of recurrent hepatitis C after LT.

Introduction

Hepatitis C virus (HCV)-related end-stage liver disease has become the leading indication for liver transplantation (LT) in Western countries. HCV recurrent infection is universal after LT in HCV-positive recipients, results in liver cirrhosis in up to 30% of the cases within 5 years from transplantation and represents a major cause of graft loss and patient death [1], [2].

Because it allows enhanced viral replication, immunosuppression has been considered as one of the main factors responsible for the accelerated course of the liver damage caused by HCV observed in liver transplant recipients. Steroids, almost universally used in association with calcineurin inhibitors in the prophylaxis of acute rejection, were believed to be possibly deleterious for HCV-positive liver transplant recipients and their use was avoided or substantially reduced in the second half of the nineties [3], [4]. However, recent reports seem to indicate that rapid steroid withdrawal can produce a negative effect on the course of recurrent hepatitis C [5], [6], [7]. In a previous retrospective study we demonstrated that slowly tapering of steroids exerted a beneficial effect on the clinical outcome of liver transplantation in HCV-positive recipients [8]. However, this finding has never been confirmed through prospective studies to date.

To confirm our previous observations and better assess the effect of steroids on the severity of recurrent hepatitis C, a prospective multicentre randomized trial was conducted.

The purpose of the study was to evaluate the incidence of biopsy-proven recurrent hepatitis C, to assess its histological and clinical severity and to correlate them with the different schedules of steroid treatment employed.

Section snippets

Study design

The study was conducted at the Liver Transplant centres of Bologna and Padua, Italy, in an open-label, not-blinded, prospective and randomized fashion.

The study protocol was approved by the Ethical Committees of the hospitals involved, and informed consent to enter the trial was obtained from each patient prior to transplantation.

HCV positive, HBsAg negative adult candidates for a first liver transplant from deceased donors using full-size grafts were considered eligible for the study.

Patients

Results

Donor (age, percentage of graft macrovescicular steatosis, cold ischemic preservation time) and recipient (age, HCV genotype, HCV-RNA serum levels) characteristics did not differ between the two groups (Table 1).

Median follow-up was 841 days (130–1376); apart from those who died or lost their graft earlier, all patients had at least a 2-year follow-up.

Nine patients died: 5/23 (21.7%) in group A of whom 4 of recurrent hepatitis C, and 4/16 (25%) in group B (all of recurrent hepatitis C).

Discussion

Chronic hepatitis C is the most common indication for liver transplantation worldwide, although the virus invariably re-infects the graft and often produces a recurrent disease. Progression of hepatitis C is much faster in graft recipients than that observed in non-transplanted patients. In the transplantation setting, as a consequence, pharmacological immunosuppression has been focused on as it can favour the replication of infectious agents by inhibiting the surveillance of the host.

Steroids

Acknowledgement

We thankfully acknowledge Astellas Pharma Italia that supported the study financially and coordinated the Centres involved.

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^☆: The authors declare that FG is employed by Astellas Pharma Italia and he coordinated the Centres involved in the study and helped in the data collection. Astellas Pharma Italia supported the study financially and coordinated the Centres involved (EPASTER Study, investigator originated and driven).

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Influence of steroids on HCV recurrence after liver transplantation: A prospective study☆

Background/Aims

Methods

Results

Conclusions

Introduction

Section snippets

Study design

Results

Discussion

Acknowledgement

J Hepatol

Liver Transpl

J Hepatol

J Hepatol

Hepatology

J Hepatol

J Hepatol

Gastroenterology

The natural history and outcome of liver transplantation in HCV-infected patients

Liver Transpl

Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up

Transplantation