Course Of Hepatitis C Virus Infection Research Articles

Treatment of Hepatitis C in the Post Liver Transplant Patient

Introduction: Hepatitis C virus (HCV) remains the most common indication for liver transplantation. Recurrence of HCV occurs in about 95% of patients after liver transplant. The course of HCV infection can be accelerated in post-transplant patients with 10-20% developing cirrhosis within five years. Successful treatment of HCV post-transplant may significantly improve overall survival of these patients. In this study, we aimed to evaluate the effects of ribavirin on treatment. Methods: A previously collected list of post-transplant patients with HCV was reviewed. The collected data included demographic information, time from transplant to treatment, viral load, treatment regimen, sustained virologic response (SVR), genotype, and pertinent laboratory values. Data were analyzed to compare SVR across different treatment regimens. Results: A total of 71 patients who underwent liver transplant at our institution were reviewed. SVR data was available for 44 at the time of the review. We treated a total of 32 male patients and 12 female patients with a mean age of 60 years. Of the 44 patients, 12 patients were treated within one year of transplant (three patients within three months). Forty of forty-four patients (91%) achieved SVR. Of the four patients who did not achieve SVR, three were treated with ledipasvir/sofosbuvir for 12 weeks (all genotype 1) and one was treated with sofosbuvir/ribavirin for 12 weeks (genotype 2b). The SVR rate for ledipasvir/sofosbuvir was 17/20 (85%) while the SVR rate for ledipasvir/sofosbuvir and ribavirin was 12/12 (100%). Ribavirin was used to treat 16 of the 44 patients. The SVR rate with ribavirin containing regimens was 15/16 (94%) vs. 25/28 (89%) without ribavirin. Of the 16 patients on ribavirin, seven (44%) had to discontinue ribavirin; five due to anemia, one due to fatigue and diarrhea, and one for unknown reasons. Thirteen of sixteen patients treated with ribavirin had genotype 1 disease and the other three had genotype 2b. Conclusion: Recurrent HCV is a common problem in the post liver transplant patient and can be a cause of significant morbidity. Successful treatment of HCV has become more common and this has been applied to the post liver transplant population. Our small series shows that high rates of SVR are possible in this population even without the addition of ribavirin. The treatment of HCV is both successful and well tolerated in the early post-transplant period.

Apolipoprotein E allele frequencies in chronic and self-limited hepatitis C suggest a protective effect of APOE4 in the course of hepatitis C virus infection.

Infectious hepatitis C virus (HCV) particles bind to host lipoproteins such as low-density lipoproteins (LDLs). Low-density lipoprotein receptors (LDLR) have been termed candidate receptors for HCV-LDL complexes. Functional host genetic single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene encoding apolipoprotein E (apoE) - a major structural LDL component and natural ligand of LDLR - likely influence the course of HCV infection. We investigated the prevalence of APOE SNPs in two large and independent cohorts of patients with chronic HCV infection compared to respective controls. We genotyped 996 chronically HCV-infected patients; 179 patients with spontaneous HCV clearance; 283 individuals with non-HCV-associated liver disease; and 2 234 healthy controls. APOE genotype proportions in patients with persistent HCV infection significantly differed from healthy controls (P = 0.007) primarily because of a substantial under-representation of APOE4 alleles in chronically HCV-infected patients (10.2%) compared to 13.0% in healthy controls (P = 0.001). The distribution of APOE4 allele positive genotypes (ε2ε4, ε3ε4, ε4ε4) also significantly differed between chronically HCV-infected patients and healthy controls (1.4%, 17%, 1% vs. 2.4%, 20.5%, 1.7%; P = 0.001), suggesting a protective effect of the APOE4 allele in HCV infection. This was confirmed by a significant over-representation of the APOE4 allele in patients with spontaneous HCV clearance (17.6%; P = 0.00008). The APOE4 allele distribution in patients with non-HCV-associated liver disease (14.0%) was very similar to healthy controls and also differed from chronically HCV-infected patients (P = 0.012), suggesting HCV specificity. Our findings suggest that the APOE4 allele may confer a protective effect in the course of HCV infection.

Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines.

Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV.

Hepatitis C and hepatocellular carcinoma: A review of natural history

The main causative factor for the chronic liver disease is infection with hepatitis C virus (HCV). Around the world, it has been estimated that almost 180 million people are carriers of HCV. Infection with HCV leads to hepatocellular carcinoma (HCC) that is a frequent cause of mortality in HCV-infected patient. Among the most common cancers, it is ranked fifth worldwide. The annually death rate of HCC patients being caused by HCV is approximately 1 million. Epidemiological studies have demonstrated that prolong infection with HCV is the main threat for the development of HCC. Keeping the knowledge about the causes of cirrhosis and development of HCC in HCV patients is consequently very important for improving treatment choices and health-care delivery. Effective precautionary measures that can prevent the progression of HCC have now been well illustrated. The perfect natural explanation of HCC pathogenesis is so diverse that treatment strategies are highly difficult. Therefore, in the case of nonmalignant hepatic disease follow-up of the patients and treatment options must take into account to prevent the progression to carcinoma. In this review, we have strived to describe natural disease course of HCV infection and the ways through which it progresses to malignant hepatic disease.

A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.

Patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (IRAK4), a critical signaling mediator in Toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll-like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor-associated factor 6, a vital step in signal transduction. Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity.

Host genetic variants influencing the clinical course of hepatitis C virus infection.

The clinical course of hepatitis C virus (HCV) infection greatly differs in individuals. Various viral, host, and environmental factors influence the natural history of HCV infection. Recent genome-wide association studies identified several host genetic factors influencing treatment efficacy or clinical course in HCV infection. A landmark discovery was that IFNL3-IFNL4 variants are strongly associated with responses to interferon-based treatment. Genetic variants in IFNL3-IFNL4 as well as those in HLA class II loci influence the spontaneous clearance of acute HCV infection. Interestingly, these genetic variants also affect the activity of hepatitis, or disease progression in chronic hepatitis C. In addition, polymorphisms in apoptosis-related genes such as RNF7, TULP1, and MERTK are associated with fibrosis progression, and DEPDC5 and MICA variants are associated with HCV-related hepatocellular carcinoma. Understanding the genetic factors associated with the clinical course of HCV infection is essential for personalized treatment and surveillance of disease progression and hepatocellular carcinoma.

Development of Serum DHCR24 Antibody as a Marker for Hepatocellular Carcinoma: The End of the Beginning

Development of Serum DHCR24 Antibody as a Marker for Hepatocellular Carcinoma: The End of the Beginning

Toll-like receptor 3 gene polymorphisms are not associated with the risk of hepatitis B and hepatitis C virus infection.

The present study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). Samples collected from HCV (n = 74) and HBV (n = 35) carriers were subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and prothrombin time (PT). A healthy control group was investigated and consisted of 299 HCV- and HBV-seronegative individuals. No significant differences in allele, genotype and haplotype frequencies were observed between the investigated groups, and no association was observed between the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305; p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels. This genetic analysis revealed the absence of an association between the polymorphisms investigated and susceptibility to HBV and HCV infection; however, these polymorphisms might be associated with a greater degree of biliary damage during the course of HCV infection.

Virological Mechanisms in the Coinfection between HIV and HCV.

Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV) is common in patients infected by Human Immunodeficiency Virus (HIV). The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

Liver disease progression in hepatitis C virus carriers with normal alanine aminotransferase levels

We read with great enthusiasm the article of Wiese et al.1 that, in our opinion, has a paramount relevance to understanding the natural history of hepatitis C virus (HCV) infection. In particular, this article does greatly in helping us to evaluate the progression to more severe liver damage of the so-called healthy HCV carriers (i.e., viremic persons with normal alanine aminotransferase [ALT] levels and liver histology). It is known that up to 30%-40% of patients with chronic HCV infection have persistently normal ALT levels,2 with many of them showing normal liver histology or minimal fibrosis. The natural course of HCV infection in these patients is not well known. Whereas some studies showed that HCV carriers with normal ALT have mild and stable disease, others reported a significant progression of fibrosis in approximately 20%-30% of such patients.3 In their first study4 describing the 20-year follow-up of over 1,000 women infected in East Germany in January 1979 by contaminated anti-D immune globulin, the researchers reported that 26 patients should be considered as true healthy carriers (i.e., normal liver, normal ALT, and persistent HCV viremia). At 25-year follow-up,5 only 11 women had remained in a healthy state, whereas the others had progressed to chronic hepatitis C (CHC). However, in this third evaluation after 35-year follow-up,1 no mention has been made about the histological and clinical status of these otherwise healthy, HCV-infected women. Thus, we wonder how many of these carriers had remained in a true healthy state 35 years after contamination and how many further carriers had progressed to CHC. Furthermore, the degree of liver damage was more or less severe in the carriers progressing to CHC with respect to other patients; were differences observed in virological response between the two groups of patients? Indeed, whether healthy HCV carriers should be offered antiviral treatment in clinical practice has been the subject of an ongoing debate.6 Introduction of the combination therapy of pegylated interferon plus ribavirin results in higher response rates,7 with a favorable risk/benefit ratio also in patients with mild or no fibrosis.8, 9 The important data of the East Germany HCV Study Group might give an answer to this unmet issue: What should we treat, the infection or the disease?10 Claudio Puoti, M.D.1 Lia Bellis, M.D.1 Olga Mitidieri Costanza, M.D.2 Maria Giuseppa Elmo, M.D.3 1Department of Internal Medicine and Liver Unit Marino General Hospital Rome, Italy 2Molecular Biology Unit Marino General Hospital Rome, Italy 3Department of Mental Health, Local Health Center Rome, Italy

Do the epidemiology, physiological mechanisms and characteristics of hepatocellular carcinoma in HIV-infected patients justify specific screening policies?

Reducing the incidence of hepatocellular carcinoma (HCC) in HIV-infected patients has become a serious problem when managing these patients. There are many explanations for this disease evolution, which notably include their longer survival under effective antiviral therapy and also the more rapid evolution of chronic liver disease. Despite recent advances in the management of hepatitis B (HBV) and hepatitis C (HCV) viral diseases, which will probably increase the number of patients achieving a virological response, HIV-infected patients with cirrhosis are still at risk of the onset of HCC. This evolution to HCC is also correlated to other comorbidities such as excessive alcohol consumption and nonalcoholic steatohepatitis (NASH). HCC thus remains a public health issue in this population. The poor prognosis and aggressiveness of HCC have been fully demonstrated, but the mechanisms underlying this aggressiveness are not yet well defined. As well as underlying mechanisms that contribute to accelerating hepatocarcinogenesis in HIV-infected patients, there are other reasons why HIV-infected patients should be considered a higher risk population. This review discusses the principal epidemiological determinants; the mechanisms of pathogenesis; and the treatment of HCC in HIV/HBV and HIV/HCV coinfected patients. It also discusses the probable need to develop a specific screening policy for HCC in this population in order to prevent the rapid development and to make them more amenable to a curative treatment.

Using patient-reported outcomes to improve the management of co-infection with HIV and HCV: the ANRS CO13 HEPAVIH cohort

The management of co-infection with HIV and hepatitis C virus (HCV) is complicated by viral and drug-drug interactions, treatment-related side effects, and the poor response to therapy of certain HCV genotypes. Current or past drug use may also have a negative impact. HEPAVIH (ANRS CO13) is an ongoing French cohort study of co-infected individuals which combines medical and socio-behavioral follow-up. This cohort study aims at analyzing the course of HCV infection and access to HCV treatment in HIV–HCV co-infected patients, using both clinical and patient-reported outcomes. This article documents the main lessons learned to date from the HEPAVIH data and published literature, while describing research prospects and needs requiring further investigation in the field of patient-reported outcomes.

Immunologic, metabolic and genetic factors in hepatitis C virus infection

The mechanisms that regulate disease progression during hepatitis C virus (HCV) infection and the response to treatment are not clearly identified. Numerous studies have demonstrated that a strong host immune response against HCV favors HCV clearance. In addition, genetic factors and metabolic machinery, particularly cholesterol modulation, are involved in HCV infection. It is likely that the interplay between all of these factors contributes to the outcome of HCV infection. In recent years, the world has experienced its largest epidemic of obesity. Mexico and the United States are the leading sufferers from this epidemic at the global level. Obesity is associated with the development of numerous pathologies including hypercholesterolemia which is one of the eight most important risk factors for mortality in Mexico. This may be related to the course of HCV infection in this population. Here, we focus on the urgent need to study the progression of HCV infection in relation to ethnic characteristics. Discoveries are discussed that hold promise in identifying immune, metabolic and genetic factors that, in conjunction, could be therapeutic targets or predictors of the progression of HCV infection.

Effect of HLA on hepatitis C virus clearance and persistence in anti-HCV-positive end-stage renal disease patients

Background/Aims:The efficacy of immune response against hepatitis C virus (HCV) is determined by human leukocyte antigen (HLA) molecules of the host which present HCV antigens to CD4 + and CD8 + T lymphocytes. In this study, we aimed to investigate the possible relationship between the frequencies of certain HLA class I–II alleles and the natural history of HCV in patients with end-stage renal disease (ESRD).Settings and Design:This is a retrospective cohort study conducted in a university hospital.Patients and Methods:The present study comprised 189 ESRD patients (candidates for renal transplantation) who had positive anti-HCV antibody test. The results concerning HCV and HLA status were gathered from patients’ files. The viral persistence was compared between the groups that were determined by HLA sub-typing.Statistical Analysis:Statistical evaluation was performed using Mann–Whitney U-test, Chi-square test, and Fisher's exact test. Level of error was set at 0.05 for all statistical evaluations, and P values < 0.05 were considered statistically significant.Results:We found possible association between the course of HCV infection and specific HLA alleles. HLA class I Cw*6 and HLA class II DRB*10 alleles were observed more frequently in the viral clearance group (P < 0.05). The HLA class I B*38 allele group was more prone to develop chronic hepatitis C (P < 0.01).Conclusions:These findings suggest that HLA class I Cw*6 and HLA class II DRB*10 alleles may be associated with immunological elimination of HCV in Turkish patients on hemodialysis. HLA sub-typing could help predict the prognosis of HCV infection.

Impact of Il28b-related single nucleotide polymorphisms on liver transient elastography in chronic hepatitis C infection.

Background and AimsRecently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography.MethodsSeven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping.ResultsCCrs12979860 was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001). Additionally CCrs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CCrs12979860 was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients.ConclusionThis study confirms previous reports that the CCrs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.

Overexpression of Regulatory T Cells Type 1 (Tr1) Specific Markers in a Patient with HCV-Induced Hepatocellular Carcinoma.

Hepatitis C virus (HCV) is an important causative agent of liver disease, but factors that determine the resolution or progression of infection are poorly understood. In this study, we suggested that existence of immunosuppressive mechanisms, supported by regulatory T cells and especially the regulatory T cell 1 subset (Tr1), may explain the impaired immune response during infection and thus the fibrosis aggravation to hepatocellular carcinoma (HCC). Using quantitative real-time PCR, we investigated the intra-hepatic presence of Tr1 cells in biopsies from a genotype 1b infected patient followed for an 18-year period from cirrhosis to HCC. We described a significant increase of gene expression in particular for the cytokines IL-10, TGF-β, and their receptors that were perfectly correlated with an increased expression of the Tr1 specific markers (combined expression of CD4, CD18, and CD49b). This was strongly marked since the patient evolved in the pathology and could explain the failure of the treatment. In conclusion, evidence of regulatory T cell installation in the liver of chronically infected patient with cirrhosis and HCC suggests for the first time a key role for these cells in the course of HCV infection.

Chronic hepatitis C in children cured of leukemia: Which management and therapy?

Background: Hepatitis C virus (HCV) is the major etiological agent of post-transfusion hepatitis. In patients cured of pediatric malignancy, chronic hepatitis C tends to run an indolent course. In contrast with these findings, cirrhosis in a cohort HCV infected cancer survivors was reported. So, we decided to evaluate the course of HCV infection and response to treatment in a cohort of children infected with HCV and cured of leukemia. Patients and methods: All children with a diagnosis of HCV infection and history of leukemia, referred to our Department of Pediatrics, were retrospectively evaluated for long-term course of HCV infection, antiviral therapy and response to treatment with pegylated-IFN alfa 2b plus ribavirin. Results: Among 185 consecutive children with diagnosis of HCV infection, 19 (12 males) had history of leukaemia (age range at diagnosis 9–15 years). All of them had received blood transfusion during cytostatic therapy. Eighteen of 19 (95%) patients presented a favourable clinical course, with sustained remission of malignant disease and presence of a mild symptom-free liver disease. After a median period of 7 years (range 2–10), a sustained virological response was observed in 6 patients treated with pegylated-IFN and ribavirin. Twelve patients remained untreated and 7 of them cleared viremia. These patients did not change their biochemical and virological status during the entire period of observation. Only a patient showed a very severe course of HCV infection requiring orthotopic liver trasplantation. This patient, at the age of 12 years, was diagnosed as affected by pre-B LLA and treated according to the National AIEOP Protocol, with remission of malignancy. Nine months later he developed a progressive liver disease. On the basis of virological markers (HCV-RNA serum levels: 3 × 106 copies/ml, genotype 1b), HCV infection was diagnosed. Liver biopsy showed chronic hepatitis. After 11 months from diagnosis of HCV infection and one month after chemotherapy discontinuation, the patient showed liver failure with jaundice, portal hypertension and hypersplenism. Liver biopsy showed HAI 9/18, stage 6, advanced cirrhosis. Treatment with ribavirin and peg-IFN-2a was started. HCV-RNA serum levels declined but the treatment was discontinued because of severe bone marrow toxicity and progressive liver failure. At the age of 15 years, the patient received a liver transplant. After this procedure, the patient showed a favourable course with absence of clinical signs of liver disease. In contrast with this favourable picture, the patient showed persistence of viremia. No predictive factor of this unfavourable outcome was identified. Conclusions: Chronic hepatitis C is usually characterized by an asymptomatic course in children cured of leukaemia. In the subset of treated patients, combination therapy with peg-IFN and ribavirin is generally associated with a favourable outcome. Nevertheless, a severe liver disease may occur in sporadic cases.

Renal involvement in HCV-related vasculitis

Renal involvement has been frequently reported in the setting of hepatitis C virus (HCV) infection. The most common renal pathology associated with chronic HCV infection is type I membranoproliferative glomerulonephritis associated with type II mixed cryoglobulinemia, while membranoproliferative glomerulonephritis without cryoglobulinemia and membranous nephropathy were less frequently reported. Rarely, focal segmental glomerulosclerosis, fibrillary and immunotactoid glomerulopathies, and thrombotic microangiopathies were described during the course of HCV infection. In the present review, we have focused on renal involvement in HCV-related vasculitis.

Performance of Molecular Methods for Hepatitis C Virus Diagnosis: Usefulness among Chronic Cases and during the Course of Infection

Molecular methods are essential to define hepatitis C virus (HCV) infection. This study was conducted to evaluate the performance of molecular qualitative and quantitative methods for HCV RNA among chronic patients and individuals during the course of HCV infection. Single serum samples were obtained from 82 HCV infected individuals where six of them donated serial serum samples (n = 52) during the course of HCV infection. Qualitative (in-house RT-nested PCR and COBAS AMPLICOR HCV Test v2.0 and TMA) and quantitative (COBAS AMPLICOR HCV Monitor Test v2.0 and bDNA) techniques were employed. TMA presented the highest rate (87.8%) of HCV detection among qualitative tests and it was the most sensitive for HCV RNA detection during the early and late phases of HCV infection. HCV RNA was quantified among 56 samples and significant correlation was observed between the two assays (r 0.92; p < 0.0001). It is concluded that both quantitative methods can be used among chronic and acute HCV cases, but TMA was the most efficient for HCV qualitative detection among chronic cases and in the early and late phases of HCV infection.

Increased Risk of Severe Hepatitis C Virus Recurrence After Liver Transplantation in Patients With a T Allele of IL28B rs12979860

Polymorphisms of the IL28B gene (encoding interferon-λ3) determine the spontaneous course of hepatitis C virus (HCV) infection and its response to antiviral therapy. We investigated the influence of the IL28B rs12979860 (C>T) polymorphism on the risk of severe HCV recurrence after liver transplantation. Ninety patients who underwent transplantation because of HCV cirrhosis were retrospectively analyzed; forty-one (45.6%) of them with severe HCV recurrence. Forty-eight of their paired donors were available and were also analyzed. IL28B rs12979860 was genotyped by real-time polymerase chain reaction, and evaluated for association with severe HCV recurrence, along with other variables, by univariate and multivariate analyses. The risk allele rs12979860-T was more common in transplanted patients (66.7%) than reported in healthy whites, and it was significantly overrepresented among patients with severe HCV recurrence, in comparison with patients without it (82.9% vs. 53.1%, odds ratio [OR]=4.30, etiologic fraction=63.6%; P=0.0028). Furthermore, separate analysis of the recipients' genotypes indicated that the risk of severe HCV recurrence increased with the dose of the T allele (linear trend, P=0.0068). Multiple logistic regression analysis confirmed the contribution of the IL28B genotype to the risk of severe HCV recurrence (OR=4.27; P=0.014), independently of other associated factors. Allele IL28B T in the donor seemed to have an opposite effect than that in the recipient (OR=0.46), but the study was underpowered to demonstrate this unforeseen effect (P=0.1995). The recipient IL28B rs12979860 genotype has a major influence on the posttransplantation course of HCV infection, being a valuable biomarker for patient care in liver transplantation.