Background. As cancer therapeutics improve, more liver transplant (LT) candidates will have a history of prior to transplant malignancy (PTM), an established risk for cancer posttransplant. Methods. This study provides granular analysis (with focus on nonliver PTM) of posttransplant cancer risk relating to PTM in 1105 consecutive adult LT recipients (2009–2019, N = 542 with PTM). Results. PTM prevalence increased from 37.8% to 63.2% during this timeframe. Post-LT survival was lower (10 y: 61.2% versus 75.1%; P < 0.001) with higher cancer-related mortality (17.6% versus 2.2%; P < 0.001) in patients with any PTM. The higher cumulative incidence of cancer post-LT associated with PTM (59.7% versus 37.6%; P < 0.001) was not attributable to de novo cancer (38.5% versus 37.7%; P = 0.21) but to recurrence. Cancer recurrence rate (10 y) was lowest in nonliver/nonskin (“other”) PTM (10.6%) with mortality rates from recurrence of only 4% in this cohort. De novo cancers may present at more advanced stage in patients with PTM and lung cancer the most common nonskin de novo malignancy (PTM 21%, no PTM 7%). Family history of cancer was an independent predictor for de novo cancer. Conclusions. PTM associated post-LT cancer outcomes are dominated by skin and liver cancer recurrence and not recurrence of “other” cancers or de novo cancer. This data supports the guidance proposals for cautious liberalization of “other” cancer remission requirements before transplantation. As post-LT cancer is highly prevalent regardless of PTM status, adherence to posttransplant cancer screening and surveillance is critical to identify early cancer after transplant.
Lack of progress in cancer-related outcomes after liver transplantation: Mitigating risk and identifying future needs to move this needle
Malignancy has a crucial impact on long-term survival after liver transplantation. There have been enhanced early detection rates with refined cancer screening and improved prognosis for many cancer diagnoses in the general population with the advent of targeted anticancer therapies. Similar advancements have not occurred in the transplant population over this same timeframe. Individualized strategies to reduce the risk of cancer are needed in this high-risk population. Strict adherence to screening and surveillance specific to the transplant population is required. Lifestyle modifications and medication management (both immunosuppressive and non-immunosuppressive) that may impact cancer risk and outcome are highlighted here. As more effective anticancer therapies evolve, transplant recipients’ access to these agents is paramount to truly impact cancer-related outcomes in this population. With adequate immunosuppression, rejection rates with immunotherapy are lower than previously purported. Prospective studies of immunosuppression modifications needed to minimize rejection and maximize cancer response are ongoing and will reduce the fear from oncology and transplant providers alike, allowing utilization of the most optimal therapy available to the individual. This review aims to assess current data to aid in clinical management and identify the need to facilitate further progress in this field.
Progression of fibrosis in liver transplant recipients with hepatitis C before and after sustained virologic response
AbstractBackground: Liver transplant (LT) recipients with untreated hepatitis C (HCV) are at risk for cirrhosis graft failure. The advent of direct acting antiviral agents (DAA) has improved outcomes in HCV.Aims: We aim to examine liver transplant outcomes and allograft fibrosis development/progression after sustained virologic response (SVR).Methods: We performed a retrospective cohort study of 226 consecutive liver transplant recipients with HCV from 2007 to 2018. The cohort was split into transplants pre (Group A) and post (Group B) 2014 to reflect the introduction of DAAs. Fibrosis was monitored with liver biopsy and non‐invasive imaging.Results: Group B had significantly improved HCV treatment rates and earlier SVR compared to Group A, with a cumulative incidence rate of SVR at 2 years of 86.7% versus 15.4% (HR = .11, p < .001). Prior to achieving SVR, Group A demonstrated worsening of fibrosis stage per year (+.21, p < .001) whereas Group B showed minimal change on protocol annual biopsy (−.02, p = .80). After SVR, most patients were followed non‐invasively and demonstrated stable or improved fibrosis stage over time. Patients undergoing transient elastography showed regression in fibrosis stage per year (−.19, p < .001).Conclusion: HCV patients undergoing LT after 2014 had higher rates of SVR and improved clinically relevant transplant outcomes, namely less graft loss and death relating to HCV. Fibrosis progression halted or improved after SVR in both cohorts, suggesting that LT recipients with SVR do not require fibrosis monitoring even with established fibrosis prior to SVR.