Hepatitis C Virus Ribonucleic Acid Test Research Articles

Assessing feasibility of a modified same-day test-and-treat model for hepatitis C among rural people who inject drugs

BackgroundDespite advancements in hepatitis C virus (HCV) treatment, low uptake among hard-to-reach populations remains a global issue. The current study aimed to assess the feasibility of a modified same-day test-and-treat model in improving HCV care for people who inject drugs (PWID) living in resource-constrained rural areas.MethodsA pilot study was conducted in four primary healthcare (PHC) centers in Malaysia. The model's key features included on-site HCV ribonucleic acid (RNA) testing using a shared GeneXpert® system; noninvasive biomarkers for cirrhosis diagnosis; and extended care to PWID referred from nearby PHC centers and outreach programs. The feasibility assessment focused on three aspects of the model: demand (i.e., uptake of HCV RNA testing and treatment), implementation (i.e., achievement of each step in the HCV care cascade), and practicality (i.e., ability to identify PWID with HCV and expedite treatment initiation despite resource constraints).ResultsA total of 199 anti-HCV-positive PWID were recruited. They demonstrated high demand for HCV care, with a 100% uptake of HCV RNA testing and 97.4% uptake of direct-acting antiviral treatment. The rates of HCV RNA positivity (78.4%) and sustained virologic response (92.2%) were comparable to standard practice, indicating the successful implementation of the model. The model was also practical, as it covered non-opioid-substitution-therapy-receiving individuals and enabled same-day treatment in 71.1% of the participants.ConclusionsThe modified same-day test-and-treat model is feasible in improving HCV care for rural PWID. The study finding suggests its potential for wider adoption in HCV care for hard-to-reach populations.

Hepatitis C care cascade in a large academic healthcare system, 2012 to 2018.

To determine the hepatitis C virus (HCV) care cascade among persons who were born during 1945 to 1965 and received outpatient care on or after January 2014 at a large academic healthcare system. Deidentified electronic health record data in an existing research database were analyzed for this study. Laboratory test results for HCV antibody and HCV ribonucleic acid (RNA) indicated seropositivity and confirmatory testing. HCV genotyping was used as a proxy for linkage to care. A direct-acting antiviral (DAA) prescription indicated treatment initiation, an undetectable HCV RNA at least 20 weeks after initiation of antiviral treatment indicated a sustained virologic response. Of the 121,807 patients in the 1945 to 1965 birth cohort who received outpatient care between January 1, 2014 and June 30, 2017, 3399 (3%) patients were screened for HCV; 540 (16%) were seropositive. Among the seropositive, 442 (82%) had detectable HCV RNA, 68 (13%) had undetectable HCV RNA, and 30 (6%) lacked HCV RNA testing. Of the 442 viremic patients, 237 (54%) were linked to care, 65 (15%) initiated DAA treatment, and 32 (7%) achieved sustained virologic response. While only 3% were screened for HCV, the seroprevalence was high in the screened sample. Despite the established safety and efficacy of DAAs, only 15% initiated treatment during the study period. To achieve HCV elimination, improved HCV screening and linkage to HCV care and DAA treatment are needed.

Disparities in the quality of care for chronic hepatitis C among Medicare beneficiaries.

PurposeChronic hepatitis C virus (HCV) infection is an important public health concern. Limited information exists on disparities in the quality of HCV care. We examine disparities in genotype or quantitative HCV ribonucleic acid testing before and after starting HCV treatment, and screening for hepatocellular carcinoma (HCC) in HCV patients with cirrhosis.MethodsThis national study included Medicare beneficiaries with HCV between 2014 and 2017. We used bivariate probit to estimate the probability of receiving recommended tests before and after HCV treatment by patient race/ethnicity, urban/rural residence, and socioeconomic status. We used multivariate logistic regression to estimate adjusted odds ratios (aOR) of HCC screening among beneficiaries with cirrhosis by patient factors.FindingsOf 41,800 Medicare patients with HCV treatment, 93.47% and 84.99% received pre- and post-treatment testing. Patients in racial minority groups had lower probabilities of pre- and post-treatment testing than whites. Rural residents were less likely to receive a post-treatment test (Coef. = -0.06, 95% CI: -0.11, -0.01). Among HCV patients with cirrhosis, 40% (24,021) received at least one semi-annual HCC screening during the study period. The odds of HCC screening were 14% lower in rural than in urban patients (aOR = 0.86, 95% CI: 0.80, 0.92), lower in African Americans (aOR = 0.93, 95% CI: 0.90, 0.96), but higher among Hispanics than in whites (aOR = 1.09, 95% CI: 1.04, 1.15). There was no significant association between ZIP-level income or education and HCC screening.ConclusionsDisparities in the quality of HCV care existed by patient race/ethnicity, urban/rural residence, and socioeconomic status. Continued efforts are needed to improve the quality of care for all HCV patients—especially rural patients and racial/ethnic minorities.

Assessing Molecular Point-of-Care Testing and Dried Blood Spot for Hepatitis C Virus Screening in People Who Inject Drugs.

BackgroundInjecting drug use is a major driver of hepatitis C virus (HCV) spread worldwide, and the World Health Organization (WHO) has identified people who inject drugs (PWID) as a key population to target for HCV screening and care. Point-of-care (POC) hepatitis C tests and dried blood spot (DBS) sampling offer benefits for the management of patients with HCV infection by increasing HCV testing and linkage to care in different nonclinical settings. The aims of this prospective study were to evaluate the feasibility and the acceptability of use HCV ribonucleic acid (RNA) POC and fingerstick DBS testing in social-medical risk-reduction centers and to describe the cascade of care among PWID in France.MethodsBetween June 2018 and February 2019, 89 consecutive HCV-seropositive PWID attending 2 drug treatment services and 1 supervised consumption room in inner Paris were invited to participate in further evaluation, undergoing a clinical review with a liver assessment and blood tests including fingerstick capillary whole blood POC HCV RNA testing and fingerstick DBS sampling.ResultsOf the 89 participants enrolled, HCV RNA was detected in 34 (38.6%) participants. Fingerstick whole blood POC RNA testing and HCV RNA detection from DBS sample were feasible and acceptable among PWID with no major difference in terms of HCV RNA detection rate. Overall, 16 participants received pan-genotypic antiviral treatment. The proportion of PWID with sustained virologic response at 12 weeks was 81.2%, with data for 3 patients still pending.ConclusionsOne-step screening strategy based on the detection of HCV RNA would engage people in care for treatment scale-up and HCV elimination.

Engaging people who inject drugs in hepatitis C virus testing and prevention through community-based outreach, in Sydney, Australia.

Increasing treatment uptake among people who inject drugs (PWID) with chronic hepatitis C virus (HCV) infection is integral to eliminating viral hepatitis. This study explored the role of community-based outreach in engaging and retaining Australian PWID in the testing component of the HCV care cascade. Semi-structured interviews were conducted with 28 PWID, including new initiates to injecting and those from culturally and linguistically diverse (CALD) backgrounds, who acquired HCV infection while enrolled in a community-based prospective observational study of hepatitis C vaccine preparedness in Sydney. Participants were interviewed at diagnosis and 12 months later. Transcripts were thematically analysed using constant comparative techniques. Community-based outreach was effective in engaging newly infected participants in HCV monitoring and decision-making about seeking interferon-based treatment. Key factors in the acceptability of outreach were privacy and discretion, and opportunities to build trust with non-judgmental staff. Retaining participants in the HCV cascade of care required more than a one-off session of post-test counselling. Ongoing discussions with staff enabled paced and tailored delivery of information about HCV prevention, testing and treatment. Increased understanding of the role of HCV ribonucleic acid viremia in determining the need for treatment, and access to this testing, was pivotal in making HCV monitoring salient for participants. Outreach is an effective strategy for engaging new initiates to injecting and CALD PWID in HCV testing and decision-making about treatment. Findings highlight the need to increase availability and access to HCV ribonucleic acid testing for PWID.

The burden of hepatitis C virus infection in Punjab, India: A population-based serosurvey.

IntroductionHepatitis C virus (HCV) infection prevalence is believed to be elevated in Punjab, India; however, state-wide prevalence data are not available. An understanding of HCV prevalence, risk factors and genotype distribution can be used to plan control measures in Punjab.MethodsA cross-sectional, state-wide, population-based serosurvey using a multi-stage stratified cluster sampling design was conducted October 2013 to April 2014. Children aged ≥5 years and adults were eligible to participate. Demographic and risk behavior data were collected, and serologic specimens were obtained and tested for anti-HCV antibody, HCV Ribonucleic acid (RNA) on anti-HCV positive samples, and HCV genotype. Prevalence estimates and adjusted odds ratios for risk factors were calculated from weighted data and stratified by urban/rural residence.Results5,543 individuals participated in the study with an overall weighted anti-HCV prevalence of 3.6% (95% Confidence Interval [CI]: 3.0%–4.2%) and chronic infection (HCV Ribonucleic acid test positive) of 2.6% (95% CI: 2.0%–3.1%). Anti-HCV was associated with being male (adjusted odds ratio 1.52; 95% CI: 1.08–2.14), living in a rural area (adjusted odds ratio 2.53; 95% CI: 1.62–3.95) and was most strongly associated with those aged 40–49 (adjusted odds ratio 40–49 vs. 19–29-year-olds 3.41; 95% CI: 1.90–6.11). Anti-HCV prevalence increased with each blood transfusion received (adjusted odds ratio 1.36; 95% CI: 1.10–1.68) and decreased with increasing education, (adjusted odds ratio 0.37 for graduate-level vs. primary school/no education; 95% CI: 0.16–0.82). Genotype 3 (58%) was most common among infected individuals.DiscussionThe study findings, including the overall prevalence of chronic HCV infection, associated risk factors and demographic characteristics, and genotype distribution can guide prevention and control efforts, including treatment provision. In addition to high-risk populations, efforts targeting rural areas and adults aged ≥40 would be the most effective for identifying infected individuals.

The Predictive Value of International Classification of Disease Codes for Chronic Hepatitis C Virus Infection Surveillance: The Utility and Limitations of Electronic Health Records.

Surveillance of chronic hepatitis C virus (HCV) cases faces limitations that result in delays and under-reporting. With increasing use of electronic health records (EHRs), the authors evaluated the predictive value of using International Classification of Diseases, Ninth Revision (ICD-9) codes to identify chronic HCV cases from EHR data. Longitudinal EHR data from 4 health care systems during 2006-2012 were evaluated. Using chart abstraction and review to confirm chronic HCV cases ("gold standard" definition), the authors calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 2 case definitions: (1) ≥2 ICD-9 codes separated by ≥6 months and (2) ≥1 positive HCV RNA (ribonucleic acid) test. Among 2,718,995 patients, 20,779 (0.8%) with ICD-9 codes indicating a likely diagnosis of chronic HCV infection were identified; 13,595 (65.4%) of these were randomly selected for review. Case definition 1 (≥2 ICD-9 codes separated by ≥6 months) had 70.3% sensitivity, 91.9% PPV, 99.9% specificity, and 99.9% NPV while case definition 2 (≥1 positive HCV RNA test) had 74.1% sensitivity, 97.4% PPV, 99.9% specificity, and 99.9% NPV. The predictive values of these alternate EHR-derived ICD-9 code-based case definitions suggest that these measures may be useful in capturing the burden of diagnosed chronic HCV infections. Their use can augment current chronic HCV case surveillance efforts; however, their accuracy may vary by length of observation and completeness of EHR data.

Implementation of a Large System-Wide Hepatitis C Virus Screening and Linkage to Care Program for Baby Boomers.

BackgroundWe implemented and evaluated a large health system-wide hepatitis C virus (HCV) screening and linkage to care program for persons born between 1945 and 1965 (“baby boomers”).MethodsAn electronic health record (EHR) clinical decision support (CDS) tool for HCV screening for baby boomers was introduced in August 2015 for patients seen in the outpatient University of California, Los Angeles healthcare system setting. An HCV care coordinator was introduced in January 2016 to facilitate linkage to HCV care. We compared HCV testing in the year prior (August 2014–July 2015) to the year after (August 2015–July 2016) implementation of the CDS tool. Among patients with reactive HCV antibody testing, we compared outcomes related to the care cascade including HCV ribonucleic acid (RNA) testing, HCV RNA positivity, and linkage to HCV specialty care.ResultsDuring the study period, 19606 participants were screened for HCV antibody. Hepatitis C virus antibody screening increased 145% (from 5676 patients tested to 13930 tested) after introduction of the CDS intervention. Screening increased across all demographic groups including age, sex, and race/ethnicity, with the greatest increases among those in the older age groups. The addition of an HCV care coordinator increased follow-up HCV RNA testing for HCV antibody positive patients from 83% to 95%. Ninety-four percent of HCV RNA positive patients were linked to care postimplementation.ConclusionsIntroduction of an EHR CDS tool and care coordination markedly increased the number of baby boomers screened for HCV, rates of follow-up HCV RNA testing, and linkage to specialty HCV care for patients with chronic HCV infection.

Improving Screening Methods for Hepatitis C Among People Who Inject Drugs: Findings from the HepTLC Initiative, 2012-2014.

People who inject drugs (PWID) are at increased risk for hepatitis C virus (HCV) infection. We examined HCV testing outcomes among PWID through CDC's Hepatitis Testing and Linkage to Care initiative, which promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites during 2012-2014. Ten grantees in nine geographically diverse cities conducted HCV testing among PWID. Among those testing positive for HCV antibody (anti-HCV), we calculated the proportion who were offered a confirmatory HCV ribonucleic acid (RNA) test, positively diagnosed, and referred to a specialist for care. We stratified anti-HCV-positive people who completed each step by same-day testing (i.e., an HCV RNA test administered on the same date as an anti-HCV test) vs. person not receiving same-day testing to evaluate whether the need for follow-up testing affected diagnosis of chronic infection and linkage to care. A total of 15,274 people received an anti-HCV test at 84 testing sites targeting PWID. Of those, 11,159 (73%) reported having injected drugs in their lifetime, 7,789 (51%) reported injecting drugs in the past 12 months, and 3,495 (23%) tested anti-HCV positive. A total of 1,630 people received testing for HCV RNA, of whom 1,244 (76%) were HCV RNA positive. When not receiving both tests on the same day, 601 of 2,465 (24%) anti-HCV-positive people received an HCV RNA test. Strategies to diagnose PWID for HCV infection are needed to reduce associated morbidity and mortality. Agencies can substantially increase the number of PWID who are diagnosed and informed of their HCV infection by administering both anti-HCV and HCV RNA tests during a single testing event.

Barriers to Treatment Among New York City Residents with Chronic Hepatitis C Virus Infection, 2014.

New, highly effective hepatitis C virus (HCV) medications recently changed the landscape of HCV treatment. Access to treatment, however, is limited. The New York City Department of Health and Mental Hygiene conducted an enhanced surveillance project to better understand the reasons patients are not treated for HCV. In June 2014, we randomly selected 300 adults who were reported through routine surveillance as having a positive HCV ribonucleic acid test result and who had seen a medical provider since June 2012. We collected information on demographics, treatment, and barriers to treatment from these 300 patients and their providers by telephone, fax, mail, and medical record review. Of 179 providers, 74 (41%) cited co-occurring conditions and 50 (28%) cited patients not keeping follow-up or referral appointments with specialists as common barriers to treatment. Forty providers (22%) reported that they do not prescribe HCV medications and instead refer patients to specialists for treatment. Of 89 patients citing barriers to treatment, 30 (34%) cited co-occurring conditions, 26 (29%) cited concerns about side effects, 21 (24%) indicated not feeling sick, 15 (17%) cited waiting for a better treatment regimen, and 12 (13%) cited medication costs or insurance issues. Only 11 providers and 10 patients denied any barriers to treatment. Increasing the number of New York City residents with HCV infection who are treated and cured will require programs to increase provider capacity, change provider behavior in treating patients with substance use and medical conditions, improve patient awareness of new medications, provide patient navigation and care coordination support through treatment, and initiate advocacy and policy work.

High-Yield Birth-Cohort Hepatitis C Virus Screening and Linkage to Care Among Underserved African Americans, Atlanta, Georgia, 2012-2013.

Hepatitis C virus (HCV) infection disproportionately affects certain populations, including those born between 1945 and 1965 (i.e., baby boomers) and African Americans. As part of the Hepatitis Testing and Linkage to Care initiative, which promoted hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites, we conducted routine HCV screening to identify previously undiagnosed, primarily African American baby boomers with chronic hepatitis C infection and link them to care. We launched the Internal Medicine Trainees Identifying and Linking to Treatment for Hepatitis C (TILT-C) initiative at the Grady Memorial Hospital Primary Care Center and Grady Liver Clinic in Atlanta, Georgia, in October 2012, and present results from the first year. TILT-C faculty implemented an electronic medical record prompt and conducted educational sessions to boost HCV screening. A project coordinator tracked testing outcomes and linked HCV-positive patients to care. Of 2,894 patients tested for anti-HCV, 201 (6.9%) tested positive. Men had a significantly higher (p<0.001) prevalence of HCV infection than women, with 106 of 1,091 (9.7%) men compared with 95 of 1,803 (5.3%) women testing anti-HCV positive. A total of 174 of 201 (86.6%) anti-HCV-positive patients received HCV ribonucleic acid (RNA) testing. Of 124 patients with a positive HCV RNA test, 122 were referred to care and 120 attended the first appointment. The TILT-C screening program was feasible and effective in detecting previously undiagnosed HCV infection and linking patients to care. The unexpectedly high prevalence of HCV infection in this primarily African American, baby boomer population underscores the need for aggressive HCV screening efforts in similar populations.

Hepatitis C Virus Testing and Linkage to Care in North Carolina and South Carolina Jails, 2012-2014.

We evaluated a hepatitis C virus (HCV) testing and linkage-to-care post-release program among detainees of small- to medium-sized jails in North Carolina and South Carolina as part of the Hepatitis Testing and Linkage to Care initiative. An HCV testing and linkage-to-care program was implemented in selected jails in North Carolina and South Carolina from December 2012 to March 2014. Health-care workers not affiliated with the jails conducted HCV antibody (anti-HCV) and HCV ribonucleic acid (RNA) testing and linkage-to-care activities. The North Carolina jail provided universal opt-out testing for HCV; South Carolina jails initially targeted high-risk individuals before expanding to routine testing. Of 669 detainees tested for HCV in North Carolina, 88 (13.2%) tested anti-HCV positive, of whom 81 (92.0%) received an HCV RNA test, 66 (81.5%) of whom tested HCV RNA positive (i.e., currently infected). Of the 66 detainees with current HCV infection, 18 were referred to HCV medical care post-release and 10 attended their first appointment. Of 224 detainees tested for HCV in South Carolina, 18 (8.0%) tested anti-HCV positive, of whom 13 received an HCV RNA test. Nine of 13 detainees tested HCV RNA positive, seven detainees were referred to post-release medical care, and two detainees attended their first appointment. Overall, 106 of 893 (11.9%) detainees were anti-HCV positive. This study demonstrated that HCV testing, identification of infection, and linkage to care are feasible among jail populations. The rate of anti-HCV positivity was lower than that found in national studies of incarcerated populations, suggesting that HCV infection prevalence in jails may vary across U.S. states or regions.

The Efficiency of Hepatitis C Virus Core Antigen Test in the Diagnosis of Hepatitis C Infection

OZ Objective: It was aimed to investigate diagnostic value of hepatitis C virus (HCV) core antigen test in patients with positive or negative anti-HCV assay by comparing with HCV ribonucleic acid (RNA) assay. Materials and Methods: Serum samples obtained from 189 patients who were admitted to Necmettin Erbakan University Meram Faculty of Medicine between December 2010 and February 2012, and HCV RNA assay were carried out for various reasons. Two mL of samples were stored under suitable conditions and antiHCV, HCV core antigen and strip immunoblot assay [Commercial INNO LIA™ HCV Score (Innogenetics NV in Ghent, Belgium)] were performed. Genotyping was performed in the amplicons of the samples with positive HCV RNA test. Results: The diagnostic sensitivity specificity, negative predictive value and positive predictive value of HCV core antigen test were 96.2%, 100%, 97.3%, and 100%, respectively. Sixty-five serum samples were genotyped and their distribution were detected: Fiftynine samples were genotype 1b, 2-genotype 1a/1b, 1-genotype 3a, 1-genotype 4, 1-genotype 2a/2c, and 1 was genotype 1a. Conclusion: It was concluded that HCV core antigen assay is highly specific, sensitive, reliable, reproducible, and easy to perform. It may be applied as a supplemental and confirmatory test in anti-HCV assays in the diagnosis of HCV.

Sustained virological response after treatment in patients with chronic hepatitis C infection - a five year follow up

Peginterferon alpha-2a and ribavirin combination therapy achieves a sustained virological response (SVR) in patients with chronic hepatitis C. Little is know about long-term durability of hepatitis C virus--Ribonucleic acid (HCV-RNA) negativity in patient treated with pegylated interferon and ribavirin therapy. Aim of this study was to evaluate the durability of virologic response in patients with SVR to anti-viral therapy treated at our centre. A total of 52 patients with chronic hepatitis C virus infection who had obtained SVR after Peginterferon alpha-2a and ribavirin combination therapy were followed up to 5 years with annual HCV-RNA testing. During this follow up period, 4 of 52 patients with initial SVR developed late relapse of hepatitis C virus infection. Relapse was more common in patients who has cirrhosis (3/6 [50%]) vs (1/46 [2.17%]) without cirrhosis. In conclusion, SVR is durable in most patients, but some patients do have late relapse; long-term follow up may be particularly important in a subset of patients with hepatitis C virus infection who have liver cirrhosis.

Cohort Profile: The International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC3) Study

The International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC(3)) Study is an international multi-cohort project of pooled biological and behavioural data from nine prospective cohorts of people who inject drugs (PWID). InC(3) brings together researchers from Australia, Canada, USA and the Netherlands with expertise in epidemiology, biostatistics, clinical and behavioural sciences, virology and immunology to investigate research questions relevant to hepatitis C virus (HCV) and HIV outcomes. InC(3) was established to: (i) create a merged multi-cohort study of pooled data from well-characterized cohorts of PWID with prospective data on HIV and HCV infections, with a particular focus on HCV; (ii) facilitate new studies not possible within individual cohorts; and (iii) bring together researchers across disciplines to answer a broad range of research questions. Study cohorts identify acute HCV cases through follow-up of high-risk HCV antibody-negative PWID or through clinical referral networks. To date, data from 1986 to 2010 have been received from all contributing cohorts, with 821 HCV-infected and 1216 HCV-uninfected participants (overall, n = 2037). Data collected include demographics, host genetics, HCV ribonucleic acid testing, alanine aminotransferase testing, HIV/hepatitis B virus testing, HCV therapy, loss to follow-up and mortality. Potential collaborators should contact the InC(3) PI Dr Kimberley Page (kPage@psg.ucsf.edu) for further information.

Viral RNA Testing in Hepatitis C Antibody–Positive Veterans

Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the U.S. population. As up to 30% of HCV-antibody (anti-HCV)-positive patients have negative HCV ribonucleic acid (RNA), indicating resolution of infection, VA (Veterans Affairs) guidelines recommend RNA testing on all anti-HCV-positive patients. As HCV RNA testing is a prequel to treatment, perceived eligibility for treatment may influence the decision to order an RNA test. This study was designed to determine the patient and healthcare facility factors associated with patient receipt of HCV RNA testing. Two logistic regression analyses were conducted in anti-HCV-positive patients, including the entire sample and then on a subsample excluding sites with routine HCV RNA testing policies, using data stored in the VA Southern California Network data warehouse. Significant patient- and site-level predictors of patient receipt of HCV RNA testing were determined. Of the 13,257 antibody-positive patients, 76% received HCV RNA testing. Excluding sites with routine HCV RNA testing, patients aged >65 years (RR=0.79) and illicit drug users (RR=0.94) were significantly less likely to receive HCV RNA testing. Patients with abnormal transaminases (RR=1.14), presence of non-HCV hepatitis (RR=1.08), or decompensated liver disease (RR=1.22) were significantly more likely to receive HCV RNA testing. Without policies for routine RNA testing, patients with hepatitic C who either are aged >65 years or are illicit drug users are less likely to be tested. Also, patient receipt of RNA testing becomes dependent on clinical cues of hepatic decompensation or inflammation. The results support the implementation of routine RNA testing for anti-HCV-positive patients.

Treatment of HCV recurrence: Do the pretransplantation rules apply?

Treatment of HCV recurrence: Do the pretransplantation rules apply?