Eliminación espontánea de virus hepatitis C en trasplantado hepático: a propósito de dos casos

The spontaneous clearance of hepatitis C virus infection is rare, especially after liver transplantation, condition in which recurrence is almost universal. We report two cases in which clearance of the virus was achieved after liver transplantation. We reviewed the literature and described possible mechanisms explaining this phenomenon, with emphasis on therapeutic implications. (Rev Med Chile 2015; 143: 663-667)

disease and hepatocellular carcinoma secondary to HCV is the main indication for liver transplantation worldwide. Recurrence and accelerated replication of HCV due to immunosuppression after liver transplantation is common and leads to decreased graft and patient survival [2,3]. Spontaneous clearance of acute hepatitis C virus (HCV) occurs in the nontransplant population at a rate of approximately 10% to 50%, usually clear HCV during first 6 month after infection, some patients experience clearance of HCV many years after chronic HCV infection has been already established [4,5]. Termination of immunosuppression, HCVspecific cellular immunity has been shown to play a critical role in the spontaneous resolution of HCV infection [6,7], acute viral infection, or immune reconstitution following receipt of HAART [8][9][10]. Spontaneous clearance of HCV is rare in the immunocompromised patients post liver transplantation. There are only few case reports about spontaneous clearance of HCV after liver and renal transplantation particularly after withdrawal of immunosuppressive agents [8,[11][12][13][14]. Here we report on the clinical features of two patients with spontaneous clearance after liver transplantation.

Case 2
A 59-year-old female patient with Hepatitis C virus-end-stage liver disease, HCC received a cadaveric liver transplantation (DDLT) on April 16, 2010. Pre-operatively, HCV RNA was 7,687 IU/ml, and HCV genotype was not reported. The patient had exploration for bleeding and sepsis due to small jejunal perforation. On May 7, 2010 HCV RNA was undetected and last HCV RNA in 31/3/2016 confirmed that it remained undetected.
Conclusion: Spontaneous clearance of HCV is rare when the patient is immunosuppressed. Here, we reported two patients with spontaneous clearance of HCV after liver transplantation. One has relapsed which highlights the need for serial testing in these patients

Background
Chronic hepatitis C is one of the main causes of chronic liver disease and estimated to affect 2-3 % of the world population, with 130-170 million people infected with HCV worldwide [1]. The outcome of HCV infection is variable and can range from minimal changes to advanced liver fibrosis and cirrhosis. End-stage liver spontaneous clearance of acute hepatitis C virus occurs in the non-transplant population at a rate of approximately 10% to 50% [5], spontaneous clearance of HCV after liver transplant is rare. Studies showed that female gender, a history of acute icteric hepatitis [16], serologic evidence of HBV coinfection [17,18], and the rs12979860 CC genotype [19][20][21][22], are variables associated with spontaneous HCV clearance.
Restoration of host immunity against HCV may be the mechanism for spontaneous HCV clearance. Lauer and Kim, propounded two conceivable scenarios for improved anti-HCV immunity: one was CD4+ and CD8+ T-cell reactivation, and the other was a massive release of type 1 IFN, which activates the dormant innate immune response. The exact mechanism for restoration of host immunity against HCV is unclear. Here we report two cases of spontaneous HCV clearance after liver transplantation. Patients were females with pre-liver transplantation viral load, both were transplanted for HCV ESLD with HCC and both patients had post-transplant sepsis treated by antibiotics and reduction of immunosuppression doses. The mechanism for spontaneous clearance of chronic HCV infection observed in our patients post-liver transplant, however, remains unclear. Reduction of immunosuppression with reconstitution of the immune system may have played a role. One patient had HCV recurrence diagnosed 2 years after spontaneous HCV clearance. One of the two patients most likely has viral relapse rather than new infection as the genotype was the same genotype before viral clearance. However, this underlines the need for long term follow up for patients with spontaneous HCV clearance. Prospective studies to identify factors associated with spontaneous HCV clearance may be difficult in the era of direct acting HCV antiviral therapy which is highly effective and well tolerated for HCV treatment as it should be given for all patients with HCV recurrence post liver transplant. Meanwhile, cases of spontaneous HCV clearance both in the transplant and nontransplant setting should be investigated in details as understanding the mechanism of HCV clearance might open new avenues for the development of future HCV therapies.