Effect of Hepatitis C Positivity on Survival in Adult Patients Undergoing Heart Transplantation (from the United Network for Organ Sharing Database)

doi:10.1016/j.amjcard.2016.04.023

The American Journal of Cardiology

Volume 118, Issue 1, 1 July 2016, Pages 132-137

https://doi.org/10.1016/j.amjcard.2016.04.023 Get rights and content

Concerns exist regarding orthotropic heart transplantation in hepatitis C virus (HCV) seropositive recipients. Thus, a national registry was accessed to evaluate early and late outcome in HCV seropositive recipients undergoing heart transplant. Retrospective analysis of the United Network for Organ Sharing registry (1991 to 2014) was performed to evaluate recipient profile and clinical outcome of patients with HCV seropositive (HCV +ve) and seronegative (HCV −ve). Adjusted results of early mortality and late survival were compared between cohorts. From 23,507 patients (mean age 52 years; 75% men), 481 (2%) were HCV +ve (mean age 52 years; 77% men). Annual proportion of HCV +ve recipients was comparable over the study period (range 1.3% to 2.7%; p = 0.2). The HCV +ve cohort had more African-American (22% vs 17%; p = 0.01), previous left ventricular assist device utilization (21% vs 14%; p <0.01) and more hepatitis B core Ag+ve recipients (17% vs 5%; p <0.01). However, both cohorts were comparable in terms of extracorporeal membrane oxygenator usage (p = 0.7), inotropic support (p = 0.2), intraaortic balloon pump (p = 0.7) support, serum creatinine (p = 0.7), and serum bilirubin (p = 0.7). Proportion of status 1A patients was similar (24% HCV + vs 21% HCV −); however, wait time for HCV +ve recipients were longer (mean 23 vs 19 days; p <0.01). Among donor variables, age (p = 0.8), hepatitis B status (p = 0.4), and Center for Diseases Control high-risk status (p = 0.9) were comparable in both cohorts. At a median follow-up of 4 years, 67% patients were alive, 28% died, and 1.1% were retransplanted (3.4% missing). Overall survival was worse in the HCV+ cohort (64.3% vs 72.9% and 43.2% vs 55% at 5 and 10 years; p <0.01), respectively. Late renal (odds ratio [OR] 1.2 [1 to 1.6]; p = 0.02) and liver dysfunction (odds ratio 4.5 [1.2 to 15.7]; p = 0.01) occurs more frequently in HCV +ve recipients. On adjusted analysis, HCV seropositivity is associated with poorer survival (hazard ratio for mortality 1.4 [1.1 to 1.6]; p <0.001). In conclusion, a small proportion of patients receiving a heart transplant in the United States have hepatitis C. Despite comparable preoperative hepatic function, hepatitis C seropositive recipients demonstrate poorer long-term survival.

Section snippets

Methods

A retrospective analysis of the United Network for Organ Sharing (UNOS) database was conducted to identify adult (≥18 years) patients undergoing first-time heart transplant from January 1991 till September 2014. Recipients were excluded if (1) they did not have relevant information regarding HCV serostatus; (2) underwent multiorgan transplant; or (3) received HCV seropositive donors. The UNOS registry records recipient and donor HCV as seropositive or seronegative; information regarding HCV RNA

Results

During the 25-year period, 23,507 consecutive patients with nonmissing hepatitis C serology underwent isolated heart transplantation (Figure 1). From this cohort, 481 (2.05%) were hepatitis C+ve (mean age 52.7 ± 11.2 years; men 77%). Ischemic and dilated cardiomyopathy was present in 38% and 35% respectively. Although 21% were listed as status 1A, 36% recipients were 1B at listing. The median wait time till transplant was 86 (26,244) days; recipients on status 1A spent 19 days, whereas 1B

Discussion

We present an adjusted analysis of isolated heart transplantation in HCV seropositive recipients over 25 years. A very small fraction of orthotropic heart transplantation recipients in the United States over the past 15 years are hepatitis C seropositive. Early mortality was significantly more in HCV+ recipients undergoing orthotropic heart transplantation. Median survival is also reduced in HCV +ve heart transplant recipients.

Chronic HCV infection remains an important bloodborne pathogen with

Disclosures

The authors have no conflicts of interest to disclose.

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Cited by (24)

Trends in the use of hepatitis C viremic donor hearts
2022, Journal of Thoracic and Cardiovascular Surgery
Citation Excerpt :
In this case, these patients may be selectively funneled to a larger institution, accounting for the significant variation within the region. Early analysis of the UNOS database before DAA therapy demonstrated increased mortality rates that were observable as early as 30 days after transplantation and persisted in long-term outcomes.4 In this study, we reevaluated 30-day mortality rates with HCV viremic hearts (2.5%) compared with HCV– donation (3.3%) and found no significant difference.
To examine trends in utilization of hearts from hepatitis C virus (HCV) viremic donors for transplantation, a strategy to expand organ availability.
The United Network for Organ Sharing (UNOS) registry was queried for adult patients undergoing heart transplantation between 2015 and 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) defined HCV status.
Between 2015 and 2019, a total of 11,393 adults underwent heart transplantation: 326 from HCV NAT⁺ donors and 11,067 from NAT⁻ donors. The use of NAT⁺ hearts increased from 1 in 2015 to 137 in 2018 against a static number of NAT⁻ organs. The use of NAT⁺ hearts varied significantly across regions and individual centers. More than 75% of NAT⁺ hearts were transplanted in the Northeast region, leading to further travel (mean, 299 miles vs 173 miles for NAT⁻ transplantations; P < .001), with longer ischemic times (mean: 3.52 hours vs 3.10 hours; P < .001). More than one-half of NAT⁺ transplantations were performed by 5 individual centers, and a single institution accounted for >20% of all transplantations from viremic donors. Survival in the 2 groups did not differ by Kaplan-Meier analysis (P = .240), and multivariable regression showed no differences in acute rejection (P = .455) or 30-day mortality (P = .490). Of the 326 recipients of NAT⁺ hearts, 38 seroconverted and 14 became viremic within 1 year. Survival was 100% in the viremic patients and 97.4% in seroconverted patients at 1 year.
Heart transplantation from HCV viremic donors continues to increase but varies significantly across UNOS regions and individual centers. Short-term outcomes are comparable, but effects of seroconversion and long-term outcomes remain unclear.
Utilization of hepatitis C virus–infected organ donors in cardiothoracic transplantation: An ISHLT expert consensus statement
2020, Journal of Heart and Lung Transplantation
Citation Excerpt :
Before the advent of DAA, several large registry-based analyses noted increased mortality following heart and lung transplantation in patients with pre-existing HCV infection relative to HCV seronegative patients undergoing transplant. Similarly, transplantation of thoracic organs from HCV seropositive donors was associated with inferior survival.13–16 Recipients of HCV seropositive hearts were more likely to die of liver disease and cardiac allograft vasculopathy.15
The advent of therapies for successful treatment of hepatitis C virus has allowed the heart and lung transplant community to re-explore the use of hepatitis C virus–positive donors for organ transplantation, with a benefit for many terminally ill patients. The consensus statements provided herein represent the current state of knowledge and expertise in this area, which we expect will continue to rapidly evolve over the next few years.
Opioid epidemic and liver disease
2019, JHEP Reports
Citation Excerpt :
While a portion of the data on kidney transplant recipients with chronic HCV who have received HCV-positive grafts have shown equivalent survival, a majority have shown poorer outcomes.192,208 Moreover, survival of both heart and lung transplant recipients with chronic HCV in whom HCV positive donors were used has uniformly been worse,209–212 though this is often in the setting of urgent transplantation and all of these studies were prior to the availability of effective anti-HCV therapy. The currently available pangenotypic DAAs have been shown to be curative in over 95% of patients infected with HCV in a variety of settings, including those with renal impairment, advanced cirrhosis, patients awaiting transplant, and perhaps most significantly, in the post-transplant period.213–224
Opioid use in the United States and in many parts of the world has reached epidemic proportions. This has led to excess mortality as well as significant changes in the epidemiology of liver disease. Herein, we review the impact of the opioid epidemic on liver disease, focusing on the multifaceted impact this epidemic has had on liver disease and liver transplantation. In particular, the opioid crisis has led to a significant shift in incident hepatitis C virus infection to younger populations and to women, leading to changes in screening recommendations. Less well characterized are the potential direct and indirect hepatotoxic effects of opioids, as well as the changes in the incidence of hepatitis B virus infection and alcohol abuse that are likely rising in this population as well. Finally, the opioid epidemic has led to a significant rise in the proportion of organ donors who died due to overdose. These donors have led to an overall increase in donor numbers, but also to new considerations about the better use of donors with perceived or actual risk of disease transmission, especially hepatitis C. Clearly, additional efforts are needed to combat the opioid epidemic. Moreover, better understanding of the epidemiology and underlying pathophysiology will help to identify and treat liver disease in this high-risk population.
AISF position paper on HCV in immunocompromised patients
2019, Digestive and Liver Disease
Citation Excerpt :
However, a recent retrospective analysis of the UNOS database (1991–2014) demonstrated that HCV positive recipients presented a worse outcome (4 years follow up) as compared to HCV negative recipients, since late renal and liver dysfunction occured more frequently in positive recipients [100]. Different mechanisms have been proposed to explain reduced survival and increase morbidity in HCV-infected cardiac recipients, such as earlier onset of cirrhosis and its complication, and accelerated coronary heart disease [101] (Table 4). In two small cohorts from single centre experiences and in a retrospective analysis of the UNOS database, the 5-year survival was similar in HCV positive and negative recipients [102–104].
Effects of Hepatitis C Virus Antibody-Positivity on Cardiac Function and Long-Term Prognosis in Patients With Adult Congenital Heart Disease
2018, American Journal of Cardiology
It was reported that hepatitis C virus (HCV) antibody-positivity adversely affects cardiac function. As the screening for HCV began in 1992, we hypothesized that HCV antibody-positive rate would be high in adult congenital heart disease (ACHD) patients who underwent heart surgery before 1992 and adversely affected cardiac function and long-term prognosis. We retrospectively enrolled 243 ACHD patients (mean age 25.9 years) who underwent cardiac surgery before 1992 and visited our hospital from 1995 to 2015. We compared clinical characteristics including cardiac function and long-term prognosis between HCV antibody-positive (n = 48) and antibody-negative (n = 195) patients. The composite end point (CEP) included cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation. The prevalence of reduced systemic ventricular ejection fraction <50% was significantly higher in the HCV antibody-positive group compared with the HCV antibody-negative group (17 vs 5.4%, p = 0.014). During a mean follow-up period of 10.1 years (interquartile range 6 to 14 years), the CEP was noted in 51 patients. Kaplan-Meier analysis showed the HCV antibody-positive group had significantly poor event-free survival than the HCV antibody-negative group (log-rank, p = 0.002). In contrast, HCV ribonucleic acid-positivity was not a significant predictor of the CEP in the HCV antibody-positive group (log-rank, p = 0.442). Furthermore, the HCV antibody-positivity was significantly associated with the CEP in both univariable and multivariable Cox regression models (hazard ratio 2.37, 95% confident interval 1.32 to 4.15, p = 0.005 and 1.96, 1.06 to 3.63, p = 0.032, respectively). In conclusion, these results suggest that more attention should be paid to HCV antibody-positivity in the management of ACHD patients.
The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation
2017, American Journal of Transplantation
The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non–HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C–infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

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: The data reported here have been supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network (OPTN). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the OPTN or the US Government.

: See page 136 for disclosure information.

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MiscellaneousEffect of Hepatitis C Positivity on Survival in Adult Patients Undergoing Heart Transplantation (from the United Network for Organ Sharing Database)

Section snippets

Methods

Results

Discussion

Disclosures

Strategies for treating chronic HCV infection in patients with cirrhosis: latest evidence and clinical outcomes

Ther Adv Chronic Dis

Natural history of hepatitis C

Gastroenterol Clin North Am

Predictors of early discontinuation of pegylated interferon for reasons other than lack of efficacy in United States veterans with chronic hepatitis C

Gastroenterol Nurs

Dilated cardiomyopathy and hypothyroidism associated with pegylated interferon and ribavirin treatment for chronic hepatitis C: case report and literature review

Braz J Infect Dis

The prevalence of hepatitis C virus infection in the United States, 1999 through 2002

Ann Intern Med

The outcome of heart transplantation in hepatitis C-positive recipients

Transplant Proc

Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates–2006

J Heart Lung Transplant

Harmful long-term impact of hepatitis C virus infection in kidney transplant recipients

Transplantation

Miscellaneous
Effect of Hepatitis C Positivity on Survival in Adult Patients Undergoing Heart Transplantation (from the United Network for Organ Sharing Database)