James F. Trotter, M.D.

Asrani, S. K., M. Kouznetsova, G. Ogola, T. Taylor, A. Masica, B. Pope, J. Trotter, P. Kamath and F. Kanwal (2018). “Increasing Healthcare Burden of Chronic Liver Disease Compared to Other Chronic Diseases, 2004-2013.” Gastroenterology. May 23. [Epub ahead of print].

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BACKGROUND & AIMS: Chronic liver disease (CLD) is a common and expensive condition, and studies of CLD-related hospitalizations have underestimated the true burden of disease. We analyzed data from a large diverse healthcare system to compare time trends in CLD-related hospitalizations with those of congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD). METHODS: We collected data from a large healthcare system in Texas on hospitalizations related to CLD (n=27,783), CHF (n=60,415), and COPD (n=34,199) from January 1, 2004 through December 31, 2013. We calculated annual hospitalization rates (per 100,000) and compared hospital course, inpatient mortality, ancillary services and re-admissions. RESULTS: Compared to patients with CHF (median age, 71 years) or COPD (median age 69 years), patients with CLD were significantly younger (median age 57 years; P<.01 vs CHF and COPD). Higher proportions of patients with CLD were uninsured (11.7% vs 5.4% for CHF and 5.4% for COPD; P<.01) and Hispanic (17% for CLD vs 9.3% for CHF and 5.0% for COPD; P<.01). A lower proportion of patients with CLD had Medicare (41.5% vs 68.6% with CHF and 70.1% with COPD; P<0.01). From 2004 through 2013, the rate of CLD-related hospitalization increased by 92% (from 1295/100,000 to 2490/100,000), compared to 6.7% for CHF (from 3843/100,000 to 4103/100,000) and 48.8% for COPD (from 1775/100,000 to 2642/100,000). During this time period, CLD-related hospitalizations covered by Medicare increased from 31.8% to 41.5%, whereas hospitalizations covered by Medicare did not change for CHF (remained at 70%) or COPD (remained at 70%). Patients with CLD had longer hospital stays (7.3 days vs 6.2 days for CHF or 5.9 days for COPD; P<.01). A higher proportion of patients with CLD died or were discharged to hospice (14.2% vs 11.5% of patients with CHF and 9.3% of patients with COPD P<.01), and a smaller proportion had access to post-acute care (13.2% vs 23.2% of patients with CHF and 27.4% of patients with COPD; P<.01). A higher proportion of patients with CLD were readmitted to the hospital within 30 days (25% vs 21.9% of patients with CHF and 20.6% with COPD; P<.01). CONCLUSIONS: Patients with chronic liver disease, compared to selected other chronic diseases, had increasing rates of hospitalization, longer hospital stays, more readmissions, and, despite these adverse outcomes, less access to post-acute care. Disease management models for chronic liver disease are greatly needed to manage the anticipated increase in hospitalizations for CLD.

Charlton, M., J. Levitsky, B. Aqel, J. O’Grady, J. Hemibach, M. Rinella, J. Fung, M. Ghabril, R. Thomason, P. Burra, E. C. Little, M. Berenguer, A. Shaked, J. Trotter, J. Roberts, M. Rodriguez-Davalos, M. Rela, E. Pomfret, C. Heyrend, J. Gallegos-Orozco and F. Saliba (2018). “International Liver Transplantation Society Consensus Statement on Immunosuppression in Liver Transplant Recipients.” Transplantation 102(5): 727-743.

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Effective immunosupression management is central to achieving optimal outcomes in liver transplant recipients. Current immunosuppression regimens and agents are highly effective in minimizing graft loss due to acute and chronic rejection but can also produce a substantial array of toxicities. The utilization of immunosuppression varies widely, contributing to the wide disparities in posttransplant outcomes reported between transplant centers. The International Liver Transplantation Society (ILTS) convened a consensus conference, comprised of a global panel of expert hepatologists, transplant surgeons, nephrologists, and pharmacologists to review the literature and experience pertaining to immunosuppression management to develop guidelines on key aspects of immunosuppression. The consensus findings and recommendations of the ILTS Consensus guidelines on immunosuppression in liver transplant recipients are presented in this article.E

Gonzalez, S. A. and J. F. Trotter (2018). “The rise of the opioid epidemic and hepatitis C-positive organs: A new era in liver transplantation.” Hepatology 67(4): 1600-1608.

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The use of hepatitis C virus (HCV)-positive organs in liver transplantation (LT) has increased in the era of direct-acting antiviral therapy. A rising demand for organs, the increased ability to effectively treat HCV infection in the transplant setting, and an unprecedented increase in HCV-positive donors have all contributed to this trend. A recent abrupt rise in opioid use in the United States has resulted in a surge of injection drug use, transmission of HCV, and opioid-related overdose deaths. Geographical areas most affected by the opioid epidemic have experienced a rapid increase in recovery and utilization of HCV-positive donor organs, in which the proportion of deceased donor LTs in the United States from donors who are HCV positive has increased nearly 2-fold within the last 3 years. The prospect of expanding the organ donor pool with HCV-positive donors and achieving acceptable posttransplant outcomes has generated much interest in the areas of liver, kidney, and thoracic transplantation, including the potential for transplanting organs from HCV positive donors into HCV-negative recipients. Developing strategies to ensure appropriate selection of potential recipients of HCV-positive organs, initiating timely antiviral therapy, and defining associated risks will be critical in achieving optimal posttransplant outcomes in this setting.

Charlton, M., J. Levitsky, B. Aqel, J. O’Grady, J. Heimbach, M. Rinella, M. Ghabril, R. Thomason, P. Burra, E. Coelho Little, M. Berenguer, A. Shaked, J. Trotter, J. Roberts, M. Rodriguez-Davalos, M. Rela, E. Pomfret and F. Saliba (2018). “International Liver Transplant Society Consensus Statement on IMMUNOSUPPRESSION IN LIVER TRANSPLANT RECIPIENTS.” Transplantation Mar 20. Epub ahead of print].

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The steady improvement in patient and graft survival rates following liver transplantation has been related to many factors, including improved efficacy of immunosuppression. Effective immunosuppression management is central to achieving optimal outcomes in liver transplant recipients. The advent of more specific, potent immunosuppression agents has, while greatly reducing graft losses through acute and chronic rejection, been associated with an increasing burden of toxicities. While dosing guidelines are available for individual immunosuppression agents, the overall approach to immunosuppression varies widely between transplant centers. The ILTS convened a consensus conference, comprised of a global panel of expert hepatologists, transplant surgeons, nephrologists and pharmacologists to develop guidelines on key aspects of immunosuppression management. Summaries of the evidence were presented to the entire group of panelists. Six broad areas of immunosuppression were addressed by the consensus panel. These topics were addressed through a critical review of the literature, followed by working group proposals and subsequent consensus, which was reviewed by the whole group. As for other ILTS guidelines, the GRADE (Grading of Recommendations Assessment Development and Evaluation) approach was used to determine the grade of the evidence and the strength of the recommendations. Quality of evidence, benefits to risk ratio, resource use and cost effectiveness were all considered in developing guidelines. Recommendations were rated according to quality of the evidence (rated as very low, low, moderate or high) and strength (rated as strong or conditional (weak)) and reflect perceived probability of benefit likely to be gained by adherence to guidance. The consensus findings and recommendations of the International Liver Transplant Society Consensus guidelines on immunosuppression in liver transplant recipients are presented in this document. The guidance, which will be updated to reflect new evidence as it becomes available, is intended for healthcare providers caring for patients before and after liver transplantation. This guidance is also intended to assist third parties in decision-making regarding access to immunosuppression regimens. (Excerpt from text, p. 5-6, in press; no abstract available.)

Charlton, M., J. Levitsky, B. Aqel, J. O’Grady, J. Hemibach, R. I. M, M. Ghabril, R. Thomason, P. Burra, E. C. Little, M. Berenguer, A. Shaked, J. Trotter, J. Roberts, M. Rodriguez-Davalos, M. Rela, E. Pomfret and F. Saliba (2018). “International Liver Transplant Society Consensus Statement on IMMUNOSUPPRESSION IN LIVER TRANSPLANT RECIPIENTS.” Transplantation. 2018 Feb 26. [Epub ahead of print]

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Immunosuppression and Malignancies: Hepatocellular carcinoma (HCC): Beyond generally minimizing overall immunosuppression, the optimal immunosuppression strategy for minimizing the frequency and severity of recurrence of HCC, including the use of mTOR inhibitors, has not been determined Skin cancers (SCCa): There is evidence that sirolimus reduces the risk of non-melanoma skin cancer recurrence in kidney transplant patients. Whether the same effects occur with everolimus, which is approved in liver transplantation, is not known but seems likely. Non-HCC, Non-SCCa malignancies: There is no direct evidence that mTOR inhibitors prevent other (non-skin, non-HCC) malignancies in liver transplant recipients, although patients with NET or RCC may benefit from everolimus-based immunosuppression. (Excerpt from text, p. 27, advanced text; no abstract available.)