Hepatitis C virus–infected women have a higher risk of advanced fibrosis and graft loss after liver transplantation than men


  • Potential conflict of interest: Nothing to report.

  • Supported by National Institutes of Health Grant T32 DK060414 (to J. C. L.) and University of California San Francisco Liver Center Grant P30 DK026743 (to N. A. T.).


In natural history studies of hepatitis C virus (HCV) infection, women have a lower risk of disease progression to cirrhosis. Whether female sex influences outcomes of HCV in the posttransplantation setting is unknown. All patients transplanted for HCV-related liver disease from 2002-2007 at five United States transplantation centers were included. The primary outcome was development of advanced disease, defined as biopsy-proven bridging fibrosis or cirrhosis. Secondary outcomes included death, graft loss, and graft loss with advanced recurrent disease. A total of 1,264 patients were followed for a median of 3 years (interquartile range, 1.8-4.7), 304 (24%) of whom were women. The cumulative rate of advanced disease at 3 years was 38% for women and 33% for men (P = 0.31), but after adjustment for recipient age, donor age, donor anti-HCV positivity, posttransplantation HCV treatment, cytomegalovirus infection and center, female sex was an independent predictor of advanced recurrent disease (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.02-1.70; P = 0.04). Among women, older donor age and treated acute rejection were the primary predictors of advanced disease. The unadjusted cumulative 3-year rates of patient and graft survival were numerically lower in women (75% and 74%, respectively) than men (80% and 78%, respectively), and in multivariable analyses, female sex was an independent predictor for death (HR, 1.30; 95% CI, 1.01-1.67; P = 0.04) and graft loss (HR, 1.31; 95% CI, 1.02-1.67; P = 0.03). Conclusion: Female sex represents an underrecognized risk factor for advanced recurrent HCV disease and graft loss. Further studies are needed to determine whether modification of donor factors, immunosuppression, and posttransplantation therapeutics can equalize HCV-specific outcomes in women and men. (HEPATOLOGY 2011;)

Natural history studies of hepatitis C virus (HCV) infection have long established that chronic liver disease progresses at unequal rates between women and men. In two large studies, each including over 1,000 HCV-infected individuals, women experienced a slower rate of fibrosis progression per year1 and a lower overall incidence of end-stage liver disease compared to men.2In vitro models supporting the antifibrinogenic effects of estrogen on hepatic stellate cells have provided a biologically plausible explanation for this sex effect in the nontransplantation setting.3, 4

Whether sex affects the outcomes of HCV-infected patients in the posttransplantation setting remains unknown. Although several studies evaluating posttransplantation outcomes have shown no significant sex effect,5-8 there is a paucity of studies specifically investigating sex differences among HCV-infected liver transplant recipients, especially with respect to risk of recurrent cirrhosis. However, a recent multicenter Italian study with long-term histological follow-up identified female sex as a risk factor for severe recurrent HCV disease.9 Moreover, a study of all liver transplantations in the United States from 1992 through 1998 found that women undergoing transplantation for HCV-related liver disease experienced increased rates of graft loss compared with women without HCV infection, whereas this difference was not evident among HCV-infected versus non–HCV-infected men10; this finding suggests that an important interaction between sex and chronic HCV infection may exist.

Identifying key recipient, donor, and transplant-related factors that affect the natural history of HCV disease posttransplantation is critical to the development of new strategies to attenuate fibrosis progression and prevent graft loss from HCV. Therefore, the Consortium to Study Health Outcomes in HCV Liver Transplant Recipients (CRUSH-C) sought to specifically examine sex differences in HCV outcomes.


CI, confidence interval; CMV, cytomegalovirus; CRUSH-C, Consortium to Study Health Outcomes in HCV Liver Transplant Recipients; HCV, hepatitis C virus; HR, hazard ratio.

Patients and Methods

Patient Population and Data Variables.

The study included all patients undergoing transplantation for HCV-related liver disease from March 1, 2002, through December 31, 2007, at five experienced transplantation centers (CRUSH-C) in the United States: the University of California–San Francisco, New York Presbyterian Hospital-Columbia, Baylor University Medical Center, the University of Colorado, and Virginia Commonwealth University. Only adult patients receiving their first liver transplant were included. HCV status was determined using anti-HCV or HCV RNA tests. Patients were excluded if they had documentation of viral clearance immediately after transplantation in the absence of posttransplantation antiviral treatment, graft loss <31 days after liver transplantation, or coinfection with human immunodeficiency virus. This study was approved by the institutional review boards at each of the five centers.

Recipient demographic and virologic data were retrospectively collected from electronic health records and manual chart review. Acute cellular rejection was defined as biopsy-proven rejection requiring treatment with high-dose bolus corticosteroids or antilymphocyte therapy. Cytomegalovirus (CMV) infection was defined as CMV infection requiring anti-CMV therapy. The dates and outcome of HCV treatment were determined by way of manual chart review, and achievement of sustained virologic response was based on documented undetectable HCV RNA at least 6 months after treatment discontinuation. Data regarding donor characteristics, warm ischemia time, and cold ischemia time were obtained from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry.


Each center used a standard immunosuppression regimen; however, immunosuppression regimens were not uniform among the sites. The specific immunosuppression-related variables collected were use of tacrolimus versus cyclosporine at last follow-up and use of corticosteroids as maintenance immunosuppression for >3 months after the date of transplantation.

Outcome Measures.

The primary outcome of our study was advanced recurrent HCV disease, which was defined as the first date of bridging fibrosis or cirrhosis on biopsy. The secondary outcome measures were (1) patient mortality, (2) graft loss, and (3) graft loss with advanced recurrent HCV disease, defined as graft loss from complications of advanced liver disease (e.g., variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis) in the setting of documented advanced fibrosis or cirrhosis. Patients without histologic follow-up were excluded from the analysis for the primary outcome, but included in the analyses for all other outcomes. Because the cause of graft loss was missing in 45/342 (13%) graft failures, a sensitivity analysis was performed assuming that all patients with an unknown cause of graft failure who had documented advanced HCV disease died from complications of advanced recurrent disease.

Statistical Analysis.

Statistical comparisons of the medians and proportions of baseline characteristics between women and men were calculated using Wilcoxon and chi-square tests, respectively. Any characteristic that was significantly different between the two groups with P < 0.05 was evaluated in the final multivariable models. Sex, the primary predictor of interest, was forced into all models.

Survival rates were computed using Kaplan-Meier methods and compared using log rank tests. Univariable Cox proportional hazards analysis was first performed to identify factors independently associated with the outcome of interest. Those variables that yielded a hazard ratio associated with P < 0.2 were evaluated for inclusion in the final multivariable model. Multivariable Cox regression models were built using backward elimination of variables that were not significantly associated with the outcome of interest using P < 0.05. Posttransplantation HCV treatment and episodes of treated acute rejection were treated as time-varying covariates. Clinically relevant interactions between sex and the following covariates—recipient age, recipient race, creatinine, hepatocellular carcinoma status, cytomegalovirus infection, episodes of rejection, and posttransplantation antiviral treatment—were evaluated in the final model at P < 0.2. To account for the effects of differing immunosuppression regimens as well as other potential unmeasured center-specific confounders, all final models were adjusted for center effect by including center as a covariable in the analyses. All tests of significance were 2-sided at P < 0.05.

Statistical analyses were performed using Stata version 11 software (Stata Corporation, College Station, TX).


Baseline Characteristics.

A total of 1,369 [334 (24%) women, 1,035 (76%) men] adult HCV-infected liver transplant recipients were initially evaluated. Thirteen (4%) women and 31 (3%) men were excluded because their graft failed within 31 days of transplantation (P = 0.42). An additional 17 (5%) women and 44 (4%) men were excluded because they were not at risk for HCV recurrence given that they were aviremic posttransplantation in the absence of antiviral treatment (P = 0.50).

Of the 1,264 patients included in the study, 304 (24%) were women and 960 (76%) were men. There was no difference in the proportion of women and men undergoing transplantation per year (data not shown). The median follow-up was 2.9 years (interquartile range, 1.6-4.4 years) for women and 3.1 years (interquartile range, 1.9-4.8 years) for men (P = 0.09). Recipient, donor, and transplant-related characteristics are listed in Table 1. Baseline recipient characteristics were comparable between sexes except for age at transplantation; proportion of Caucasian, Hispanic, or Asian race; proportion undergoing living donor liver transplantation; and proportion having hepatocellular carcinoma at the time of transplantation. Women were more likely to receive a sex-mismatched allograft than men, but other donor characteristics including age, African American race, and HCV status were similar. Rates of treated acute rejection differed significantly between the two groups: 80 (26%) women versus 190 (20%) men required at least one bolus of corticosteroids, but 8 (3%) women versus 36 (4%) men were treated at least once with antilymphocyte therapy. Other characteristics evaluated but not significantly different between the two groups included body mass index at transplantation, cold ischemic time, and immunosuppressive medication at last follow-up.

Table 1. Baseline Characteristics of HCV-Infected Liver Transplant Recipients and Their Donors
CharacteristicsWomen (n = 304)Men (n = 960)P Value
  • Abbreviations: IQR, interquartile range; MELD, model for end-stage liver disease; No., number; CMV, cytomegalovirus.

  • Data are presented as no. (%) unless noted otherwise.

  • *

    Treated with either pulse-dosed steroids or anti-lymphocyte therapies.

  • Of the patients who received anti-HCV therapy after transplantation.

Recipient characteristics   
 Age, median (IQR), years53.4 (49.1-59.0)53.0 (49.0-56.6)0.02
  Caucasian172 (57)648 (68)0.001
  Hispanic70 (23)166 (17)0.03
  African American37 (12)88 (9)0.13
  Asian13 (4)17 (2)0.01
  Other12 (4)41 (4)0.87
 Living donor liver transplant30 (10)56 (6)0.02
 Body mass index, median (IQR)27.6 (24.2-31.5)27.6 (24.9-31.1)0.89
 Laboratory MELD score at transplantation, median (IQR)18 (14-24)18 (13-23)0.38
 Hepatocellular carcinoma93 (31)423 (44)<0.001
Donor characteristics   
 Age, median (IQR), years42 (25-53)41 (26-52)0.73
 African American race41 (14)130 (14)0.99
 Positive for hepatitis C antibody20 (7)71 (8)0.61
 Male sex139 (47)627 (67)<0.001
 Cold ischemic time, median (IQR), hours7.5 (5.3-9.5)7.7 (5.6-9.6)0.32
Posttransplantation characteristics   
 Maintenance immunosuppression medications   
  Tacrolimus use at last follow-up178 (59)603 (63)0.18
  Cyclosporine use at last follow-up75 (25)260 (27)0.41
  Corticosteroids at last follow-up142 (47)407 (42.4)0.19
 No. of episodes of treated acute rejection*  0.03
  0217 (71)742 (77) 
  157 (19)172 (18) 
  ≥230 (10)46 (5) 
 Posttransplantation anti-HCV treatment96 (32)285 (30)0.53
 Sustained virologic response22 (23)69 (24)0.80
 CMV infection32 (11)124 (13)0.27

Advanced Disease.

Biopsy data were available for 90.6% of patients, with an equal proportion of women and men missing biopsy data (8.9% and 9.6%, respectively; P = 0.72). Both women and men had a median of three biopsies per patient (P = 0.82). The median times to first biopsy were similar between women and men (112 days versus 130 days; P = 0.93) as were the median times from the first biopsy to the subsequent biopsy documenting advanced fibrosis (or, for patients who did not have advanced fibrosis, to the last biopsy) (456 days versus 458 days; P = 0.60).

The median time to advanced fibrosis was 4.6 years for women compared with 5.2 years for men (P = 0.31 [log rank]). Of the patients with available biopsy data, the cumulative rates of advanced disease at 1, 3, and 5 years were 6%, 38%, and 54%, respectively, for women compared with 8%, 33%, and 45%, respectively, for men in unadjusted analysis. However, after adjustment for other factors associated with advanced fibrosis, women had a significantly higher rate of advanced recurrent HCV disease relative to men (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.02-1.70; P = 0.04) (Table 2; Fig. 1). Other independent predictors of advanced disease were older recipient age, older donor age, positive donor HCV antibody, and treated CMV infection (Table 2). Receipt of posttransplantation antiviral treatment prior to advanced fibrosis was protective (Table 2). In an exploratory analysis of factors associated with advanced fibrosis among female transplant recipients, the most important predictors were donor age (HR per year, 1.01; 95% CI, 1.00-1.03; P = 0.07) and treated acute rejection before advanced fibrosis (HR, 1.56; 95% CI, 1.00-2.46; P = 0.05).

Table 2. Univariable and Multivariable Analyses of Predictors Associated with Advanced Fibrosis
CovariatesUnivariable* HR (95% CI)P ValueMultivariable HR (95% CI)P Value
  • *

    Includes all covariates associated with the outcome with a P value <0.2. Sex, the predictor of interest, was forced into the model.

  • Other covariates that were evaluated were: renal function, cold/warm ischemia time, hepatitis B virus coinfection, donor sex, and episodes of rejection before fibrosis.

  • Adjusted for center effect.

  • Compared with deceased donor liver transplant.

Recipient female sex1.14 (0.89-1.46)0.311.32 (1.02-1.71)0.04
Recipient age (per year)0.98 (0.96-0.99)0.0080.98 (0.96-0.998)0.03
Recipient African American race1.61 (1.18-2.20)0.003
Living donor transplant0.62 (0.36-1.05)0.08
Hepatocellular carcinoma0.77 (0.61-0.97)0.03
Donor age (per 10 years)1.22 (1.14-1.30)<0.0011.24 (1.15-1.33)<0.001
Donor cause of death (stroke/other)1.47 (1.18-1.85)0.001
Positive donor HCV antibody1.80 (1.22-2.66)0.0031.51 (1.01-2.26)0.046
Posttransplantation antiviral treatment before advanced fibrosis0.61 (0.46-0.80)<0.0010.73 (0.54-0.99)0.04
Treated CMV infection1.78 (1.34-2.37)<0.0011.70 (1.26-2.31)0.001
Figure 1.

Adjusted rates of advanced fibrosis by sex in HCV-infected liver transplant recipients.


Death occurred in 308 (24.4%) patients with significantly more women (28.6%) dying compared with men (23.0%) (P = 0.048). Cumulative rates of survival at 1, 3, and 5 years posttransplantation were 87%, 75%, and 66%, respectively, for women and 92%, 80%, and 73%, respectively, for men (P = 0.04 [log rank]). On univariable analysis, we observed an increased risk of death for women compared with men (HR, 1.30; 95% CI, 1.01-1.67; P = 0.04), and this significant difference persisted after adjustment for other factors associated with survival (Table 3).

Table 3. Multivariable Analyses of Predictors Associated with Mortality and Overall Graft Loss
CovariatesGraft Loss*,, HR (95% CI)P ValueMortality*,, HR (95% CI)P Value
  • *

    Adjusted for center effect.

  • All covariables that were associated with the outcome with P < 0.2 in univariable analysis were evaluated for inclusion in the multivariable analysis. Sex, the predictor of interest, was forced into the model.

  • Other covariates that were evaluated were: renal function, living versus deceased donor transplantation, donor cause of death, positive donor HCV antibody, cold/warm ischemia time, HBV coinfection, donor sex, and episodes of rejection before fibrosis.

Recipient female sex1.31 (1.02-1.67)0.031.33 (1.03-1.72)0.03
Recipient age (per year)1.02 (1.00-1.04)0.02
Recipient African American race1.44 (1.03-2.00)0.031.56 (1.11-2.19)0.01
Serum creatinine at transplantation1.11 (1.00-1.22)0.0451.11 (1.01-1.23)0.04
Donor age (per 10 years)1.20 (1.12-1.29)<0.0011.21 (1.13-1.30)<0.001
Receipt of posttransplantation antiviral treatment0.64 (0.49-0.84)0.0010.56 (0.42-0.75)<0.001
Treated CMV infection1.63 (1.24-2.16)0.0011.59 (1.18-2.14)0.002

Overall and HCV-Specific Graft Survival.

Graft failure occurred in 93 (31%) women and 249 (26%) men during the study period (P = 0.11). Compared with men, women experienced a trend toward decreased graft survival at 1 (87% versus 90%), 3 (74% versus 78%), and 5 years (71% versus 64%) (P = 0.08 [log rank]). On univariable analysis, a similar trend was seen with female sex associated with a 23% increased risk of graft loss (HR, 1.23; 95% CI, 0.97-1.57; P = 0.09). After adjustment for other recipient, donor, and transplant-related factors in multivariable models, the association between female sex and graft failure increased, with a 33% increased risk of graft failure compared with male sex and was statistically significant (Table 3; Fig. 2). Among female recipients, donor age (HR per year, 1.01; 95% CI, 1.00-1.03; P = 0.02) and treated CMV infection (HR, 1.89; 95% CI, 1.08-3.30; P = 0.03) emerged as independent predictors of graft loss.

Figure 2.

Adjusted rates of graft survival by sex in HCV-infected liver transplant recipients.

The reason for graft failure was known for 297/342 (87%) of graft failures. There were equal proportions of unknown causes of graft failure between women and men (13% for both; P = 0.93). Of the recipients whose cause of graft failure was known, 39 (13%) women and 83 (9%) men experienced graft failure with advanced recurrent HCV disease (P = 0.02). Cumulative rates of graft survival free from advanced HCV disease at 1, 3, and 5 years were 97%, 91%, and 82% for women compared with 97%, 92%, and 88% for men (P = 0.02 [log rank]). In multivariable models of graft failure with advanced HCV disease, women experienced a substantially increased risk of graft failure with advanced HCV disease (HR, 1.71; 95% CI, 1.14-2.58; P = 0.01). A sensitivity analysis was performed assuming that all patients with an unknown cause of graft failure who had documented advanced HCV disease died from complications of advanced recurrent disease. In this analysis, the female sex effect was somewhat attenuated (HR, 1.39; 95% CI, 0.94-2.05; P = 0.10).

Association Between Recipient Sex, Donor Sex, and Outcomes.

Detailed evaluation of the association between recipient sex, donor sex, and each outcome was performed. On univariable analysis, donor female sex was not significantly associated with advanced fibrosis, mortality, overall graft failure, or HCV-specific graft failure (Table 4). Bivariable analyses were then used to assess the contribution of recipient sex and donor sex together on each outcome. In these analyses, donor sex was again not significantly associated with each of the four outcomes, but there was a trend toward a significant association between donor female sex and HCV-specific graft failure (Table 4). Finally, on multivariable analyses, there was no association between donor sex and advanced fibrosis, mortality, or graft failure. However, donor sex was associated with a 41% decreased risk of HCV-specific graft failure (HR, 0.59; 95% CI, 0.39-0.89; P = 0.01) and was therefore included in the final multivariable model.

Table 4. Univariable, Bivariable, and Multivariable Analyses of the Association Between Recipient Sex, Donor Sex, and Outcomes
OutcomeUnivariableP ValueBivariableP Value
Advanced fibrosis    
 Recipient female sex1.14 (0.89-1.46)0.301.15 (0.89-1.49)0.28
 Donor female sex1.00 (0.80-1.26)0.980.98 (0.77-1.24)0.86
 Recipient female sex1.30 (1.01-1.66)0.041.31 (1.01-1.69)0.04
 Donor female sex1.10 (0.87-1.39)0.411.05 (0.83-1.33)0.67
Overall graft loss    
 Recipient female sex1.23 (0.97-1.57)0.091.25 (0.98-1.60)0.08
 Donor female sex1.04 (0.83-1.30)0.721.00 (0.80-1.26)0.99
HCV-specific graft loss    
 Recipient female sex1.56 (1.06-2.27)0.021.72 (1.16-2.56)0.007
 Donor female sex0.77 (0.52-1.14)0.200.70 (0.47-1.04)0.08


In this large, multicenter cohort study of 1,264 United States patients undergoing transplantation for HCV-related liver disease, rates of advanced recurrent disease, mortality, and overall and HCV-specific graft loss were significantly higher in women than in men. In addition, recipient female sex was consistently found to be an independent predictor of each of these four clinically relevant outcomes. Our results confirm and extend the findings of Belli et al,9 who initially reported this sex difference in recurrent HCV disease in a study that included 93 women from three centers in Italy. Further validation of our findings is a recently published analysis of United Network for Organ Sharing data from the post-MELD era by Thuluvath et al.11 in which HCV-infected women experienced an increased risk of death compared with HCV-infected men. Importantly, our large, United States–based center-level study, which includes detailed biopsy data and posttransplantation events (e.g., episodes of acute rejection, HCV treatment), offers a potential explanation for this sex difference in mortality: women die more frequently than men secondary to more aggressive recurrent HCV.

Although women were slightly older than men at transplantation, had an increased likelihood of undergoing living donor transplantation, lower rates of hepatocellular carcinoma, and higher rates of acute rejection, our multivariable analyses demonstrate that these differences alone did not account for the sex difference in outcomes. Nor did donor sex significantly affect the association between recipient sex and outcomes in either bivariable or multivariable analyses, with the exception of HCV-specific graft loss where female donor sex strengthened the female recipient sex effect. Furthermore, because there were no sex differences among those who were excluded from our study for early graft loss (<31 days) or HCV aviremia, cohort selection bias is less likely to have contributed to the observed female sex effect.

Our findings may reflect a sex-specific etiologic effect on HCV-disease progression. Epidemiologic studies have shown that women infected with chronic HCV experience slower fibrosis progression and lower rates of cirrhosis than men.1, 12 Liver transplantation may naturally select for those women with chronic HCV who have genetic, virologic, and immunologic factors that lead to a higher risk of cirrhosis and also more rapidly progressive disease posttransplantation. Our study was not designed to test this hypothesis, but studies of HCV-infected patients evaluating women with cirrhosis versus women without cirrhosis may shed further light on this issue.

Regardless of etiology, understanding the specific factors contributing to this sex difference is critical to improving posttransplantation outcomes for all HCV-infected recipients. Our findings suggest that women may need to be monitored more closely for disease progression than under current practice. In particular, given our analyses demonstrating that donor age and treated acute rejection are the dominant predictors of poor outcome among women, women receiving older donor liver grafts who have had early acute rejection may need to be targeted for earlier posttransplantation antiviral therapy or receive less aggressive treatment for acute rejection.

Interestingly, we found that antiviral therapy prior to the development of advanced fibrosis was associated with a 27% decreased risk of advanced fibrosis compared with patients who did not receive antiviral therapy prior to this outcome. Although some studies have reported that the benefit of posttransplantation antiviral treatment in HCV-infected liver transplant recipients is generally limited to those who achieve sustained virologic response,13, 14 exploratory analyses of our data revealed that the protective effect was independent of sustained virologic response. Furthermore, antiviral therapy in the posttransplantation setting in our cohort was protective against death and graft loss, a finding that is similar to the survival benefit seen in other more recently published studies.15, 16 Although we found no significant differences in the baseline characteristics of the patients who received treatment compared with those who did not, whether our findings represent a true protective effect of treatment as opposed to a bias toward treating healthier patients certainly warrants further investigation. Additionally, caution in interpreting these treatment-related associations in our study is needed, as we lack detailed information regarding dose, duration, and tolerability of antiviral therapy in the treated patients, and these factors may influence treatment benefits.

There are several limitations to our study. Certain posttransplantation metabolic factors, notably diabetes, have been shown to be important predictors of recurrent disease progression; however, accurate information on posttransplantation diabetes and insulin resistance are difficult to ascertain in a retrospective study such as ours. Second, the cause of graft failure was missing in 13% of our cohort, but without any evidence of a selection bias by sex. Our sensitivity analysis confirmed a hazard of similar direction and magnitude of HCV-specific graft failure associated with female sex, and this does not change the association between sex and overall graft failure that we observed. In addition, although liver biopsies were not performed as part of a standard protocol among each of the five centers, there were no sex differences in the median number of biopsies, time to the first biopsy, and time from the first biopsy to the biopsy showing advanced fibrosis, so it is unlikely that this limitation accounts for the sex effect. These limitations underscore the importance of a developing a future prospective multicenter study to confirm our findings using this retrospective cohort as a stepping stone.

We acknowledge that there are inherent limitations to this multicenter study owing mainly to the heterogeneity of the centers' practices for posttransplantation care with respect to immunosuppression and HCV treatment. We carefully evaluated cyclosporine versus tacrolimus-based regimens in our multivariable models and found that their effect on the association between sex and each of the four outcomes was qualitatively similar to models that were adjusted for center effect. Therefore, we elected to adjust each multivariable model for center effect alone, because this statistical technique has the advantage of accounting for such recognized differences in addition to other potential confounders that we could not measure directly.

However, the multicenter nature of this study is also its strength. CRUSH-C is the largest and most contemporary cohort to examine sex effects on the natural history of HCV following transplantation. Given the relatively small numbers of outcomes among the female subgroup of HCV-infected transplant recipients, other smaller, single-center studies have been extremely limited in performing adjusted analyses to assess the relationship between female sex and HCV-specific outcomes.

In conclusion, female sex represents an important risk factor for advanced recurrent HCV disease and graft loss. Our retrospective study provides provocative evidence to support a long-term, prospective cohort study using standard immunosuppression regimens, protocol liver biopsies, and posttransplantation treatment algorithms to determine whether modification of donor factors, immunosuppression, and posttransplantation therapeutics may serve to equalize HCV-specific outcomes in women and men. Clearly, sex is important in posttransplantation outcomes for HCV-infected liver transplant recipients, but whether sex-specific algorithms for posttransplantation management can optimize outcomes remains to be determined.