Receipt of a living donor liver transplant (LDLT) has been associated with improved survival compared with waiting for a deceased donor liver transplant (DDLT). However, the survival benefit of liver transplant has been questioned for candidates with model for end-stage liver disease (MELD) scores< 15, and the survival advantage of LDLT has not been demonstrated during the MELD allocation era, especially for low MELD patients. Transplant candidates enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study after 02/28/02 were followed for a median of 4.6 years. Starting at the time of presentation of the first potential living donor, mortality for LDLT recipients was compared to mortality for patients who remained on the waiting list or received DDLT (no LDLT group) according to categories of MELD score (<15 or 15+) and diagnosis of hepatocellular carcinoma (HCC). Of 868 potential LDLT recipients (453 with MELD<15; 415 with MELD 15+ at entry), 712 underwent transplantation (406 LDLT; 306 DDLT), 83 died without transplant, and 73 were alive without transplant at last follow-up. Overall, LDLT recipients had 56% lower mortality (hazard ratio (HR)=0.44, 95% confidence interval [CI] 0.32–0.60; p<0.0001). Among candidates without HCC, mortality benefit was seen both with MELD<15 (HR=0.39;p=0.0003) and MELD 15+ (HR=0.42;p=0.0006). Among candidates with HCC, a benefit of LDLT was not seen for MELD<15 (HR=0.82, p =0.65) but was seen for MELD 15+ (HR=0.29, p=0.043).

Conclusions

Across the range of MELD scores, patients without HCC derived a significant survival benefit when undergoing LDLT rather than waiting for DDLT in the MELD liver allocation era. Low MELD candidates with HCC may not benefit from LDLT.

In natural history studies of hepatitis C virus (HCV) infection, women have a lower risk of disease progression to cirrhosis. Whether gender influences outcomes of HCV in the post-transplant setting is unknown. All patients transplanted for HCV-related liver disease from 2002–2007 at 5 U.S. transplant 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. 1,264 patients were followed for a median of 3.0 years (IQR 1.8–4.7) −304 (24%) were female. The cumulative rate of advanced disease at 3-years was 38% for females and 33% for males (p=0.31) but after adjustment for recipient age, donor age, donor anti-HCV positivity, post-transplant HCV treatment, cytomegalovirus infection and center, female gender was an independent predictor of advanced recurrent disease (HR, 1.31; 95%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 females than males, 75% vs. 80% and 74% vs. 78%, and in multivariable analyses, female gender 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 gender represents an under-recognized risk factor for advanced recurrent HCV disease and graft loss. Further studies are needed to determine whether modification of donor factors, immunosuppression, and post-transplant therapeutics can equalize HCV-specific outcomes in women and men.

Introduction

Information on long-term health among living liver donors is incomplete. Because changes in standard laboratory tests may reflect underlying health among donors, pre- and post- donation results were examined in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL).

Methods

A2ALL followed 487 living liver donors who donated at nine U.S. transplant centers between 1998 and 2009. Aminotransferase and alkaline phosphatase activities (AST, ALT, AP), bilirubin, INR, albumin, white blood cell count (WBC), hemoglobin, platelet count, ferritin, serum creatinine and BUN were measured at evaluation and post-donation: 1 week, 1 month, 3 months, 1 year and yearly thereafter. Repeated measures models were used to estimate median lab values at each time point and test for differences between values at evaluation (baseline) and post-donation time points.

Results

Platelet counts were significantly decreased at every time point compared to baseline, and at three years were 19% lower. Approximately 10% of donors had a platelet count ≤150 (×1000/mm3) at 2–3 years post-donation. Donors with a platelet count ≤150 (×1000/mm3) at one year had had significantly lower mean platelet counts (189±32) vs. the remainder of the cohort (267±56, p<0.0001) at evaluation. Statistically significant differences from evaluation were noted for AST, AP, INR and albumin through the first year, although most measurements were in the normal range. Median values for WBC, hemoglobin, ferritin, albumin, serum creatinine, BUN, and INR were not substantially outside the normal range at any time point.

Conclusions

After three months, most laboratory values return to normal among right hepatic lobe liver donors, with slower return to baseline levels for AST, AP, INR and albumin. Persistently decreased platelet counts warrant further investigation.

Some studies have found that donor-recipient gender mismatch predicts post-transplant outcomes but whether this is independent of donor quality is unknown. To evaluate the association between gender mismatch and graft loss, 11,508 females(F) and 16,714 males(M) who underwent liver transplant from 3/1/2002-12/31/2007 were studied. Of 11 donor characteristics, clinically relevant differences between F and M donors were median age (47 vs. 39yrs), height (165 vs. 178cm), and proportion dying of stroke (59 vs. 35%) [p<0.001 for all]. The donor risk index was significantly lower for F than M donors (1.3 vs. 1.6, p<0.001). Recipients of gender mismatched grafts had an 11% higher risk of graft loss (p<0.001). Compared to M→M donor-recipient matched transplants in univariable analysis, F→M mismatch was associated with a 17% increased risk of graft loss (95%CI=1.11-1.24, p<0.001), whereas M→F mismatch was not (HR=1.02; 95% CI=0.96-1.09; p=0.46). However, adjustment for significant recipient and donor factors eliminated the association between F→M mismatch and graft loss (HR=0.95; 95%CI=0.89-1.02; p=0.18). In conclusion, donor quality differs significantly between female and male donors – female donors are older, shorter, and die more frequently of stroke – and gender differences in donor quality, rather than gender mismatch are predictive of graft loss.

This study examined factors associated with the gender disparity in wait-list mortality in the MELD era. Adult patients listed for liver transplantation from 2002-2008 were included. Females [12,585(36%)] and males [22,126(64%)] differed clinically by age (54 vs. 52 years), height (1.6 vs. 1.8 meters), listing estimated glomerular filtration rate [eGFR; 70 vs. 83 ml/min], and cirrhosis etiology. Holding MELD constant, females were at 19% (95%CI, 1.13-1.25, p<0.001) higher risk of wait-list mortality than males under the current allocation system. The relative hazard increased with worsening renal function, whether measured by serum creatinine or eGFR. Adjustment for MELD, age, African-American race, cirrhosis etiology, region, and ABO group attenuated this relative hazard (HR 1.16; 95%CI, 1.10-1.22; p<0.001) but additional adjustment for height completely explained this gender disparity in wait-list mortality (HR 1.05; 95%CI, 0.98-1.12; p=0.2). Transplantation rates, however, remained lower among females, even after adjustment for height (HR 0.88; 95%CI, 0.82-0.92; p<0.001). In conclusion, under the current liver allocation system, women have a 19% increased risk of wait-list mortality compared to men with the same MELD scores. Height contributes to this gender disparity, possibly reflecting differences in transplantation rates for shorter individuals.

Background

Complications of hepatitis C virus (HCV) infection are primarily related to the development of advanced fibrosis.

Methods

Baseline data from a prospective community-based cohort study of 204 persons with chronic hepatitis C virus (HCV) infection were used for analysis. The outcome was fibrosis score on biopsy and the primary predictor evaluated was daily cannabis use.

Results

The median age of the cohort was 46.8 years, 69.1% were male, 49.0% were Caucasian, and the presumed route of infection was injection drug use in 70.1%. The median lifetime duration and average daily use of alcohol were 29.1 years and 1.94 drink equivalents per day. Cannabis use frequency (within prior 12 months) was daily in 13.7%, occasional in 45.1%, and never in 41.2%. Fibrosis stage, assessed by Ishak method, was F0, F1–2 and F3–6 in 27.5%, 55.4% and 17.2% of subjects, respectively. Daily compared to non-daily cannabis use was significantly associated with moderate to severe fibrosis (F3–6 versus F1–2) in univariate [OR = 3.21 (95% CI, 1.20–8.56), p = 0.020] and multivariate analyses (OR = 6.78, (1.89–24.31), p=0.003). Other independent predictors of F3–6 were ≥11 portal tracts (compared to <5, OR = 6.92 (1.34–35.7), p=0.021] and lifetime duration of moderate and heavy alcohol use [OR per decade = 1.72 (1.02–2.90), p=0.044].

Conclusion

We conclude that daily cannabis use is strongly associated with moderate to severe fibrosis and that HCV-infected individuals should be counseled to reduce or abstain from cannabis use.

In this retrospective study of hepatitis C virus (HCV)–infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT (P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT ≤20) compared to later cases (LDLT > 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients (P < 0.001 and P = 0.008, respectively). Graft and patient survival in LDLT >20 and DDLT were not significantly different (P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT >20, and LDLT ≤20 were 80%, 79% and 55%, with similar results conditional on survival to 90 days (84%, 87% and 68%, respectively). Predictors of graft loss beyond 90 days included LDLT ≤20 vs. DDLT (hazard ratio [HR] = 2.1, P = 0.04), pretransplant hepatocellular carcinoma (HCC) (HR = 2.21, P = 0.03) and model for end-stage liver disease (MELD) at transplantation (HR = 1.24, P = 0.04). In conclusion, 3-year graft and patient survival in HCV-infected recipients of DDLT and LDLT >20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation.

Background

Fibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times.

Methods

We used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR) quantified the estimated effects of covariates on progression risk at any given time.

Results

Models estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018), and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002). When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80). There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059). Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection.

Discussion

The analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating active disease and high risk, while longer time already spent in a stage indicates quiescent disease and low risk.

Objective

To compare rates of hospitalization before and after adult-to-adult living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT).

Summary background data

LDLT recipients have been reported to have lower mortality but a higher complication rate than DDLT recipients. The higher complication rate may be associated with greater consumption of inpatient hospital resources and a higher burden of disease for LDLT recipients.

Methods

Data from the 9-center Adult-to-Adult Living Donor Liver Transplantation (A2ALL) retrospective cohort study were analyzed to determine pre-transplant, transplant, and post-transplant hospitalizations among LDLT candidates (potential living donor was evaluated) who received LDLT or DDLT. Hospital days and admission rates for LDLT and DDLT patients were calculated per patient-year at risk, starting from the date of initial potential donor history and physical examination. Rates were compared using overdispersed Poisson regression models.

Results

Among 806 candidates, 384 received LDLT and 215 received DDLT. In addition to the 599 transplants, there were 1913 recipient hospitalizations (485 pre-transplant; 1428 post-transplant). Mean DDLT recipient pre-transplant, transplant, and post-transplant lengths of stay were 5.8±6.3, 27.0±32.6, and 9.0±14.1 days, respectively, and for LDLT were 4.1±3.7, 21.4±24.3, and 7.8±11.4 days, respectively. Compared to DDLT, LDLT recipients had significantly lower adjusted pre-transplant hospital day and admission rates, but significantly higher post-transplant rates. Significantly higher LDLT admission rates were observed for biliary tract morbidity throughout the second post-transplant year. Overall hospitalization rates starting from the point of potential donor evaluation were significantly higher for eventual recipients of LDLT.

Conclusions

LDLT recipients, despite lower acuity of disease, have higher hospitalization requirements when compared to DDLT recipients. Continuing efforts are warranted to reduce the incidence of complications requiring post-LDLT inpatient admission, with particular emphasis on biliary tract issues.

Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multi-racial cohort of US women with high prevalence of HCV and HIV. Our primary analyses evaluated associations between twelve HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1–2.6), B*5701 (PR=2.0; 95% CI = 1.0–3.1), B*5703 (PR = 1.7; 95% CI = 1.0–2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0–3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), while DRB1*0301 (PR = 0.4; 95% CI = 0.2–0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2–11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (IDU; N=838), but no significant relationships were observed.

Conclusion

HLA genotype influences host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance since they were a priori hypothesized.

Multistate modeling methods are well-suited for analysis of some chronic diseases that move through distinct stages. The memoryless or Markov assumptions typically made, however, may be suspect for some diseases, such as hepatitis C, where there is interest in whether prognosis depends on history. This paper describes methods for multistate modeling where transition risk can depend on any property of past progression history, including time spent in the current stage and the time taken to reach the current stage. Analysis of 901 measurements of fibrosis in 401 patients following liver transplantation found decreasing risk of progression as time in the current stage increased, even when controlled for several fixed covariates. Longer time to reach the current stage did not appear associated with lower progression risk. Analysis of simulation scenarios based on the transplant study showed that greater misclassification of fibrosis produced more technical difficulties in fitting the models and poorer estimation of covariate effects than did less misclassification or error-free fibrosis measurement. The higher risk of progression when less time has been spent in the current stage could be due to varying disease activity over time, with recent progression indicating an “active” period and consequent higher risk of further progression.

Abstract

Although the primary mode of hepatitis C virus (HCV) transmission is exposure to blood products or injection drug use (IDU), studies have found varying independent risk factors for HCV infection among persons with no history of IDU or exposure to blood products. For HIV-infected women, sexual transmission may be another potential source of HCV infection. HIV-infected and HIV-negative women at risk for HIV enrolled in the Women's Interagency HIV Study (WIHS) during October 1994 to November 1995 and again between October 2001 and November 2002 were studied. Clinical and demographic factors associated with HCV seroprevalence were assessed in multivariate logistic regression models controlling for history of blood transfusion and IDU. Among 3636 women with HCV results, 31.5% were HCV antibody positive (HCV+) including 13.5% with no reported history of IDU or blood transfusions. Multivariate logistic regression analyses stratified on IDU showed that among women with no history of IDU, sex with an IDU male was independently associated with HCV positivity (odds ratio [OR] = 2.8, 95% confidence [CI] = 2.1, 3.8, p < 0.0001) after controlling for blood transfusion, age, HIV infection, unemployment, birth in the United States, history of hepatitis B infection, and current smoking status. Further stratification on HIV status showed that the association was significant only for the HIV+ (OR = 1.9, 95% CI = 1.3, 2.7, p = 0.0007) compared to the HIV− women (OR = 1.1, 95% CI = 0.4, 2.7) although these odds ratios were not significantly different (p = 0.25). For HIV-positive women with no reported history of IDU, sex with an IDU male was independently associated with HCV suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women.

BACKGROUND & AIMS

In the last decade, significant progress has been made in the treatment of liver disease associated with chronic hepatitis, especially in patients infected with the hepatitis B virus (HBV). To investigate whether the population-wide application of antiviral therapies has impacted liver transplant waiting list registration, we analyzed longitudinal trends in waiting list registration for patients with hepatitis B and C and those with nonviral liver disease.

METHODS

This study represented a retrospective analysis of registry data containing all US liver transplant centers. All adult, primary liver transplantation candidates registered to the Organ Procurement and Transplantation Network between 1985 and 2006 were included in the analysis. Standardized incidence rates were calculated for waiting list registration for liver transplantation by underlying disease (HBV and HCV infection and other) and by indication for transplantation (fulminant liver disease, hepatocellular carcinoma [HCC], and end-stage liver disease [ESLD]).

RESULTS

Of 113,927 unique waiting list registrants, 4793 (4.2%) had HBV, and 40,923 (35.9%) had HCV infections; the remaining 68,211 (59.9%) had neither. The incidence of waiting list registration for ESLD and fulminant liver disease decreased, whereas that for HCC increased. The decrease in ESLD registration was most pronounced, and the increase in HCC was least dramatic among registrants with hepatitis B. The decrease in registration for ESLD secondary to HCV infection was also significantly larger than that for ESLD patients with non-viral etiologies.

CONCLUSIONS

The pattern of liver transplantation waiting list registration among patients with hepatitis B suggests that the widespread application of oral antiviral therapy for HBV contributed to the decreased incidence of decompensated liver disease.

Organ procurement in China has been criticized because of its reliance on executed prisoners as donors. We aimed to assess the influence of perceptions about organ procurement practices in China on domestic patient care decisions.

Methods

An anonymous Internet administered case-based questionnaire was used to survey an sample of healthcare professionals with affiliations to hepatology and transplantation professional societies.

Results

Of 674 completed surveys, the vast majority (93%) of the respondents were physicians, surgeons or allied transplant professionals actively caring for liver transplant patients and 81% practiced in the United States (US). A strong majority believed procurement practices were ethically sound in the US and Europe (87% and 73%) but fare fewer believed that procurement practices were ethically sound in China (4%, p<0.001). In case-based questions, lack of confidence in the ethical standards of organ procurement in China predicted patient-care decisions. The majority would provide post-transplantation care for patients who underwent liver transplantation at another domestic center, in a foreign country and in China (90%,78%,63%, respectively, p<0.001) yet respondents who suspected unethical procurement practices in China were more reluctant to do so (p<0.001).

Conclusions

Transplant professionals expressed concern about organ procurement practices in China which influenced their patient care decision-making.

Although the primary mode of hepatitis C virus (HCV) transmission is exposure to blood products or injection drug use (IDU), studies have found varying independent risk factors for HCV infection among persons with no history of IDU or exposure to blood products. For HIV-infected women, sexual transmission may be another potential source of HCV infection. HIV-infected and HIV-negative women at risk for HIV enrolled in the Women’s Interagency HIV Study (WIHS) during October 1994 to November 1995 and again between October 2001 and November 2002 were studied. Clinical and demographic factors associated with HCV seroprevalence were assessed in multivariate logistic regression models controlling for history of blood transfusion and IDU. Among 3636 women with HCV results, 31.5% were HCV antibody positive (HCV+) including 13.5% with no reported history of IDU or blood transfusions. Multivariate logistic regression analyses stratified on IDU showed that among women with no history of IDU, sex with an IDU male was independently associated with HCV positivity (odds ratio [OR] = 2.8, 95% confidence [CI] = 2.1, 3.8, p < 0.0001) after controlling for blood transfusion, age, HIV infection, unemployment, birth in the United States, history of hepatitis B infection, and current smoking status. Further stratification on HIV status showed that the association was significant only for the HIV+ (OR = 1.9, 95% CI = 1.3, 2.7, p = 0.0007) compared to the HIV− women (OR = 1.1, 95% CI = 0.4, 2.7) although these odds ratios were not significantly different ( p = 0.25). For HIV-positive women with no reported history of IDU, sex with an IDU male was independently associated with HCV suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women.

Introduction

Pure red cell aplasia due to anti-epoetin antibodies is a known complication of epoetin therapy for anemia due to chronic kidney disease. This disease has not previously been well described in the setting of therapy for chronic hepatitis C virus infection. While treatment for pure red cell aplasia due to anti-epoetin antibodies is usually with immunosuppressive therapy such as calcineurin inhibition, the safety of this treatment in chronic hepatitis C virus infection is unknown. To date, little has been published on the efficacy of rituximab on pure red cell aplasia due to anti-epoetin antibodies.

Case presentation

This report describes a 65-year-old Asian-American woman who developed pure red cell aplasia from high titer neutralizing anti-epoetin antibodies after epoetin-alfa therapy during ribavirin and peg-interferon treatment for chronic hepatitis C virus infection. We describe the outcome of her treatment with rituximab. The reticulocyte count increased, and anti-epoetin antibody titer decreased with a loss of neutralizing activity in vitro, leading to a reduction in blood transfusions, and eventual resolution of anemia, without reactivation of hepatitis C virus.

Conclusion

The diagnosis of pure red cell aplasia from anti-epoetin antibodies should be considered in patients undergoing therapy for chronic hepatitis C virus infection who develop severe anemia after administration of erythropoietin or darbepoetin. Though it is currently an off-label indication, rituximab is a therapeutic option for patients with pure red cell aplasia due to anti-epoetin antibodies.

Background & Aims

The relationship between serum peginterferon pharmacokinetics and pharmacodynamics and the early virologic response (EVR) to peginterferon and ribavirin therapy was assessed in patients with chronic hepatitis C virus (HCV) genotype 1 infection in the Virahep-C study.

Methods

333 patients [160 African Americans (AA) and 173 Caucasian Americans (CA)] who received peginterferon alfa-2a (180 μg/wk) without a dose modification during the initial 4 weeks of therapy were analyzed. Peginterferon and 2,5-OAS serum levels were measured on days 0, 1, 2, 3, 7, 14, 28, 56, 84, and 168 of treatment. The EVR: (≥ 2 log10 decline in HCV RNA levels by week 12 of therapy) was the primary virologic endpoint.

Results

Peginterferon pharmacokinetics after the first dose were similar in AA and CA, but AA had greater peginterferon concentrations at days 1, 3, 14 and 28 (p < 0.05). AA had higher absolute serum 2,5-OAS levels on days 0, 1, 2, 3, 7, 14, 28 and 56 (p < 0.05), but the magnitude of 2,5-OAS induction during treatment relative to day 0 were similar. AA patients exhibited a smaller decline in serum HCV RNA during the first 28 days of treatment (p < 0.001) and a lower EVR (65% vs. 83%). AA and CA with EVR had significantly higher serum peginterferon concentrations and serum 2,5-OAS induction during the first 12 weeks than patients without an EVR.

Conclusion

Peginterferon alfa-2a pharmacokinetic and pharmacodynamic variability is associated with EVR in both AA and CA with HCV infection, but do not explain the racial disparity in combination treatment efficacy.

In this multicenter evaluation, the VERSANT HCV RNA 3.0 Assay (bDNA) (Bayer Diagnostics, Tarrytown, N.Y.) was shown to have excellent reproducibility, linearity, and analytical sensitivity across specimen collection matrices (serum, EDTA, ACD-A), and hepatitis C virus (HCV) genotypes 1 to 6. The VERSANT HCV bDNA Assay has a reportable range of 615 to 7,690,000 (7.69 × 106) IU/ml. The total coefficient of variation (CV) ranged from 32.4% at 615 IU/ml to 17% at 6.8 × 106 IU/ml. The assay was linear across the reportable range. Analytical specificity of 98.8% was determined by testing 999 specimens from volunteer blood donors. Evaluation of HCV genotypes using RNA transcripts of representative clones of 1a, 1b, 2a, 2b, 2c, 3a, 4a, 5a, and 6a and patient specimens showed that the largest difference between genotype 1, upon which the assay is standardized, and non-1 genotypes was within 1.5-fold. Testing of potentially interfering endogenous substances and exogenous substances and conditions found no interference in HCV-positive or HCV-negative specimens except for unconjugated bilirubin at concentrations of ≥20 mg/dl and protein at concentrations of ≥9 g/dl. Biological variability was estimated from 29 clinically stable individuals not on HCV therapy who were tested weekly over an 8-week period. The combined estimate of total (biologic plus assay) variability was 0.15 log10 standard deviation (CV, 36.1%), a fold change of 2.6. Thus, the observed fold change between any two consecutive HCV RNA measures is expected to be less than 2.6-fold (equivalent to 0.41 log10 IU/ml) 95% of the time in clinically stable individuals.