Daytime variation in hepatitis C virus replication kinetics following liver transplant.

Xiaodong Zhuang,Ian Rowe,Peter Balfe,Jane A Mckeating,Alvina G Lai

doi:10.12688/wellcomeopenres.14696.1

Xiaodong Zhuang, Ian Rowe + Show 3 more

Open Access

https://doi.org/10.12688/wellcomeopenres.14696.1

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Abstract

Background: There is a growing interest in the role of circadian regulated pathways in disease pathogenesis. Methods: In a cohort of hepatitis C virus (HCV) infected patients undergoing liver transplantation, we observed differences in early viral infection kinetics of the allograft that associated with the time of liver transplant. Results: A higher frequency of subjects transplanted in the morning showed a rebound in viral RNA levels (n=4/6) during the first week post-surgery. In contrast, no viral rebound was observed in seven subjects transplanted in the afternoon. None of the other parameters previously reported to influence viral replication in the post-transplant setting, such as donor age, cold-ischemia time and length of surgery associated with viral rebound. Conclusions: These observation highlights a role for circadian processes to regulate HCV infection of the liver and warrants further investigation.

Highlights

The circadian clock is an evolutionarily conserved biological time-keeping system that synchronizes behavioural and physiological processes to a 24-hour cycle, including cell proliferation and metabolism[1]
In a cohort of hepatitis C virus (HCV) infected patients undergoing liver transplantation, we observed differences in early viral infection kinetics of the allograft that associated with the time of liver transplant
To investigate whether HCV replication kinetics is influenced by the time of transplant, patients in the untreated arm of the trial were grouped according to their time of surgery between the hours 6am–1pm (AM) (n=6) or 2pm–11pm (PM) (n=7)

Summary

Introduction

The circadian clock is an evolutionarily conserved biological time-keeping system that synchronizes behavioural and physiological processes to a 24-hour cycle, including cell proliferation and metabolism[1]. In four of six patients (#3, 7, 8 and 11) in the AM group, a viral rebound toward pre-transplant levels was observed during the time of study (Figure 2A). None of the seven patients transplanted in the PM group showed a recovery of viral load to pre-transplant levels (Figure 2B). Methods: In a cohort of hepatitis C virus (HCV) infected patients undergoing liver transplantation, we observed differences in early viral infection kinetics of the allograft that associated with the time of liver transplant. None of the other parameters previously reported to influence viral replication in the post-transplant setting, such as donor age, cold-ischemia time and length of surgery associated with viral rebound. Conclusions: These observation highlights a role for circadian processes to regulate HCV infection of the liver and warrants further investigation

Methods

Results

Conclusion