Erika D. Lease

Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Symptomatic Respiratory Virus Infection and Chronic Lung Allograft Dysfunction

Our data demonstrate that symptomatic respiratory virus infection is strongly associated with development of chronic lung allograft dysfunction. With multiple new respiratory antivirals currently in clinical trial, this association offers a potentially intervenable risk factor for a highly morbid process.

Posttraumatic stress disorder in organ transplant recipients: a systematic review.

OBJECTIVE To summarize and critically review the existing literature on the prevalence of posttraumatic stress disorder (PTSD) following organ transplantation, risk factors for posttransplantation PTSD and the relationship of posttransplant PTSD to other clinical outcomes including health-related quality of life (HRQOL) and mortality. METHODS We conducted a systematic literature review using PubMed, CINAHL Plus, the Cochrane Library and PsycInfo and a search of the online contents of 18 journals. RESULTS Twenty-three studies were included. Posttransplant, the point prevalence of clinician-ascertained PTSD ranged from 1% to 16% (n=738), the point prevalence of questionnaire-assessed substantial PTSD symptoms ranged from 0% to 46% (n=1024) and the cumulative incidence of clinician-ascertained transplant-specific PTSD ranged from 10% to 17% (n=482). Consistent predictors of posttransplant PTSD included history of psychiatric illness prior to transplantation and poor social support posttransplantation. Posttransplant PTSD was consistently associated with worse mental HRQOL and potentially associated with worse physical HRQOL. CONCLUSIONS PTSD may impact a substantial proportion of organ transplant recipients. Future studies should focus on transplant-specific PTSD and clarify potential risk factors for, and adverse outcomes related to, posttransplant PTSD.

Risk Factors and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infection in Solid Organ Transplant Recipients

Background Ganciclovir-resistant (ganR) cytomegalovirus (CMV) is an emerging and important problem in solid organ transplant (SOT) recipients. Only through direct comparison of ganR- and ganciclovir-sensitive (ganS) CMV infection can risk factors and outcomes attributable specifically to ganciclovir resistance appropriately be determined. Methods We performed a retrospective, case-control (1:3) study of SOT recipients with genotypically confirmed ganR-CMV (n = 37) and ganS-CMV infection (n = 109), matched by donor/recipient CMV serostatus, year and organ transplanted, and clinical manifestation. We used χ2 (categorical) and Mann-Whitney (continuous) tests to determine predisposing factors and morbidity attributable to resistance, and Kaplan-Meier plots to analyze survival differences. Results The rate of ganR-CMV was 1% (37/3467) overall and 4.1% (32/777) among CMV donor-positive, recipient-negative patients, and was stable over the study period. GanR-CMV was associated with increased prior exposure to ganciclovir (median, 153 vs 91 days, P < .001). Eighteen percent (3/17) of lung transplant recipients with ganR-CMV had received <6 weeks of prior ganciclovir (current guideline-recommended resistance testing threshold), and all non-lung recipients had received ≥90 days (median, 160 [range, 90-284 days]) prior to diagnosis of ganR-CMV. GanR-CMV was associated with higher mortality (11% vs 1%, P = .004), fewer days alive and nonhospitalized (73 vs 81, P = .039), and decreased renal function (42% vs 19%, P = .008) by 3 months after diagnosis. Conclusions GanR-CMV is associated with longer prior antiviral duration and higher attributable morbidity and mortality than ganS-CMV. Upcoming revised CMV guidelines should incorporate organ transplant-specific thresholds of prior drug exposure to guide rational ganR-CMV testing in SOT recipients. Improved strategies for prevention and treatment of ganR-CMV are warranted.

Cryptococcosis in patients with cirrhosis of the liver and posttransplant outcomes

Background The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known. Methods We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care. Results In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%. Conclusions Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.

Successful Treatment of Scopulariopsis Infection in a Lung Transplant Recipient

A 42-year-old underwent bilateral lung transplant for bronchiectasis due to primary ciliary dyskinesia. By 5weeks posttransplant, he was found to have significant mucosal necrosis at the bronchus intermedius with a green–black discoloration seen. Cultures from many bronchoalveolar lavage and tissue samples did not reveal any fungus. However, because of the high suspicion for fungal infection even with negative cultures, he was treated with voriconazole and inhaled amphotericin. Despite ongoing antifungal treatment, over the subsequent months, he developed recurrent stenosis of the bronchus intermedius requiring frequent rigid bronchoscopies and dilations. Twelve months posttransplant, a culture from a biopsy of the grayish-black tissue revealed Scopulariopsis brevicaulis. Susceptibility testing for this isolate subsequently revealed resistance to most agents, with minimum inhibitory concentrations for voriconazole of 16mg/mL, posaconazole 2mg/mL, amphotericin B>6mg/mL, and terbinafine>2mg/ mL, with relative susceptibility to micafungin at 0.25mg/ mL. Hewas empirically treatedwith both posaconazole and terbinafine, and after 4 months of therapy, the submucosal discoloration was better, the stenosis was improved, and his need for dilations decreased dramatically. Combination treatment was continued for 18 months with complete resolution of the infection. Over 18 months after completion of treatment, he remains well without evidence of chronic lung allograft dysfunction, recurrent airway stenosis, or other complications of his Scopulariopsis infection.

Medical Management of the Lung Transplant Recipient: Extrapulmonary Issues

Following transplantation, medical management of the lung transplant recipient is vital for maintaining the health of the allograft and to promote an overall successful outcome after a lung transplant surgery. This includes vigilant and meticulous monitoring for all lung transplant-related issues, including administering appropriate immunosuppression with antirejection medications while monitoring for associated toxicities and drug interactions as well as prompt detection of infection and lung allograft rejection. In addition, there must be full awareness of the many non-pulmonary complications that may arise following lung transplantation, a large number of which are related to immunosuppressant effects or toxicities. Non-pulmonary complications include but are not limited to renal dysfunction, hematologic abnormalities, gastrointestinal complications, neurologic sequelae, oncologic manifestations, and metabolic derangements. While monitoring lung allograft function following transplantation is critical to overall survival, monitoring of the subsequent non-pulmonary complications is also important to avoid increased morbidity and mortality in lung transplant recipients. The lung transplant pulmonologist must assume the role of a very thorough internist for the lung transplant recipient in order to monitor and address the many complications occurring after lung transplantation. This chapter focuses on the medical management of non-pulmonary issues in the lung transplant recipient.

Management of Cellular and Humoral Rejection: Prevention, Diagnosis, and Treatment

Acute cellular and antibody-mediated (humoral) rejections are two forms of acute rejection seen following lung transplantation. The management of acute cellular and antibody-mediated rejection is complex and may be individualized based on the unique situation of each patient. The prevention of acute cellular rejection starts with induction immunosuppression and frequent clinical monitoring as well as through the management of potential risk factors such as gastroesophageal reflux disease and various infections. Antibody-mediated rejection is less understood and requires further study. The mainstay of treatment for acute cellular rejection as well as antibody-mediated rejection is through the augmentation of immunosuppression through a variety of medical strategies. The management of acute cellular rejection and antibody-mediated rejection is important due to the associations with the development of chronic lung allograft dysfunction, the primary cause of mortality following lung transplantation. With optimal management and further study, the goal is for improved survival and quality of life for all lung transplant recipients.

ISHLT Consensus Statement on adult and pediatric airway complications after lung transplantation: Definitions, grading system, and therapeutics

Airway complications remain a major cause of morbidity and mortality after cardiothoracic transplantation. The reported incidence of airway ischemic complications varies widely, contributed to by the lack of a universally accepted grading system and standardized definitions. Furthermore, the majority of the existing classification systems fail to integrate the wide range of possible bronchial complications that may develop after lung transplant. Hence, a Working Group was created by the International Society for Heart and Lung Transplantation with the aim of elaborating a universal definition of adult and pediatric airway complications and grading system. One such area of focus is to understand the problem in the context of a more standardized consensus of classifying airway ischemia. This consensus definition will have major clinical, therapeutics, and research implications.

Solid Organ Transplantation From Hepatitis B Virus-Positive Donors: Consensus Guidelines for Recipient Management: Transplantation From Hepatitis B Virus-Positive Donors

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.