Virology and pathogenesis of hepatitis C virus recurrence

Ramírez, Santseharay; Pérez‐del‐Pulgar, Sofía; Forns, Xavier

doi:10.1002/lt.21644

Cited by 52 publications

(33 citation statements)

References 47 publications

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“…Under strong purifying selection in patient C, HCV achieved stable adaptation to the host that could be sustained for ϳ7 years. This observation indicates that, despite HCV-specific immune responses causing HVR1 diversification, the HCV intrahost evolution may significantly slow down to levels reported in immunocompromised patients (7,26,41).…”

Section: Vol 85 2011 Intrahost Evolution Of Hepatitis C Virus 6375mentioning

confidence: 86%

Temporal Variations in the Hepatitis C Virus Intrahost Population during Chronic Infection

Ramachandran

Campo

Dimitrova

et al. 2011

J Virol

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The intrahost evolution of hepatitis C virus (HCV) holds keys to understanding mechanisms responsible for the establishment of chronic infections and to development of a vaccine and therapeutics. In this study, intrahost variants of two variable HCV genomic regions, HVR1 and NS5A, were sequenced from four treatment-naïve chronically infected patients who were followed up from the acute stage of infection for 9 to 18 years. Median-joining network analysis indicated that the majority of the HCV intrahost variants were observed only at certain time points, but some variants were detectable at more than one time point. In all patients, these variants were found organized into communities or subpopulations. We hypothesize that HCV intrahost evolution is defined by two processes: incremental changes within communities through random mutation and alternations between coexisting communities. The HCV population was observed to incrementally evolve within a single community during approximately the first 3 years of infection, followed by dispersion into several subpopulations. Two patients demonstrated this pattern of dispersion for the rest of the observation period, while HCV variants in the other two patients converged into another single subpopulation after ϳ9 to 12 years of dispersion. The final subpopulation in these two patients was under purifying selection. Intrahost HCV evolution in all four patients was characterized by a consistent increase in negative selection over time, suggesting the increasing HCV adaptation to the host late in infection. The data suggest specific staging of HCV intrahost evolution.Hepatitis C virus (HCV) infection is a major cause of liver disease in the world. It is estimated that ϳ130 million people are infected with HCV globally (2). HCV is a heterogeneous single-stranded (plus-strand) RNA virus belonging to the Flaviviridae. The HCV genome contains one large open reading frame that encodes a polyprotein which can be processed into 10 mature proteins (34). HCV causes chronic infection in 70 to 85% of infected adults. There is no vaccine against HCV, and current antiviral therapy is effective in only 50 to 70% of chronically infected patients (18).HCV intrahost evolution is frequently compared to an "arms race," implying that the HCV genome constantly changes in order to escape from neutralizing adaptive immunoresponses (53). This concept of constant change is seemingly different from the HIV model, according to which intrahost evolution slows down with CD4 ϩ T-cell depletion and quasispecies diversity decreases with the development of AIDS (48). Our limited understanding of the dynamics of HCV intrahost evolution impedes the development of efficient therapeutic and prophylactic interventions.Analysis of HCV longitudinal evolution is significantly hindered by difficulties with identifying and with long-term follow-up of patients, starting from the acquisition of infection. In the present study, we explored HCV evolutionary processes during long-term chronic infection in four treatment-...

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Section: Vol 85 2011 Intrahost Evolution Of Hepatitis C Virus 6375mentioning

confidence: 86%

Temporal Variations in the Hepatitis C Virus Intrahost Population during Chronic Infection

Ramachandran

Campo

Dimitrova

et al. 2011

J Virol

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“…This setting has provided a unique model to study the viral kinetics and the source of HCV infection of the graft, the effect of LT on the role of the viral quasispecies in HCV transmission, and whether viral evolution may determine the outcome of hepatitis C recurrence. 141 The evidence so far accumulated indicates that LT represents a bottleneck for the viral population because only a reduced number of the preexisting variants are able to infect the graft. Consequently, newly infected individuals typically contain a significantly more homogeneous viral population than before LT, as evidenced as early as 4 days after LT, and even more markedly 3 weeks later.…”

Section: Hcv Quasispecies and Liver Transplantationmentioning

confidence: 99%

New Insights into the HCV Quasispecies and Compartmentalization

Farci

2011

Semin Liver Dis

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Hepatitis C virus (HCV) is a hepatotropic RNA virus with an extraordinary propensity to persist in the vast majority of infected individuals. During replication, because of the inherent infidelity of the viral RNA polymerase, each progeny RNA genome contains mutations that lead to a continuous diversification of the viral population. Consequently, HCV circulates in vivo as a quasispecies, which is a dynamic distribution of divergent but closely related genomes subjected to a continuous process of genetic variation, competition, and selection. This genomic heterogeneity confers a remarkable advantage to the viral population allowing for a rapid adaptation to a changing environment when the virus is subject to selective constraints exerted by the host, such as antiviral immunity, or external to the host, such as antiviral therapy. The large reservoir of variants provided by the quasispecies represents a great challenge for the control of HCV infection and has important biologic implications for viral persistence, host cell tropism, antiviral drug resistance, and development of an HCV vaccine. This review discusses the molecular mechanisms of HCV genetic variation and the biologic and clinical relevance of the quasispecies nature of HCV.

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“…HCV-cirrhosis is the most frequent indication for liver transplantation (LTx) in Europe and America [2] . Although accepted as the standard of care for end-stage liver disease [3] , the progression of liver disease is variable, leading to re-transplantation and lower survival rates. Because of these results, concerns have been expressed regarding the appropriateness of re-transplantation for HCV and the optimal timing of surgery in an era of organ shortage [4] .…”

Section: Introductionmentioning

confidence: 99%

Strategies to reduce hepatitis C virus recurrence after liver transplantation

Ciria

Pleguezuelo²,

Khorsandi³

et al. 2013

WJH

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Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not retransplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pretransplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of posttransplant HCV recurrence and strategies to reduce its impact on our patients.

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Virology and pathogenesis of hepatitis C virus recurrence

Cited by 52 publications

References 47 publications

Temporal Variations in the Hepatitis C Virus Intrahost Population during Chronic Infection

Temporal Variations in the Hepatitis C Virus Intrahost Population during Chronic Infection

New Insights into the HCV Quasispecies and Compartmentalization

Strategies to reduce hepatitis C virus recurrence after liver transplantation

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