James F. Trotter, M.D.

Asrani, S. K., G. Saracino, J. G. O’Leary, S. Gonzales, P. Kim, G. McKenna, G. Klintmalm and J. Trotter (2018). “Recipient characteristics and morbidity and mortality after liver transplantation.” J Hepatol. Feb 14. [Epub ahead of print].

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BACKGROUND: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States. METHODS: We sought to identify a parsimonious set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within 5 years after liver transplantation using national (n=31,829, 2002-2015) and center specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (5 pts; HR 1.59, 95% CI 1.48-1.72); recipient age >60 years (3 pts; HR 1.29, 95% CI 1.23-1.36); hemodialysis (3 pts; HR 1.26, 95% CI 1.16-1.37); diabetes (2 pts; HR 1.20, 95% CI 1.14-1.27); or serum creatinine >/=1.5mg/dL without hemodialysis (2 pts; HR 1.15, 95% CI 1.09-1.22). RESULTS: Graft survival within 5 years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with > 8 points, graft survival was 42% (MELD<25) and 50% (MELD 25-35) in recipients receiving donors with donor risk index >1.7. In center specific data within the first year, subjects with >/= 5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p<0.01), higher admissions for rehabilitation (12.3% versus 2.7%, p<0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p<0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p=0.03) within 5 years. CONCLUSION: The impact of co-morbidities in a MELD based organ allocation system needs to be reassessed. The proposed clinical tool may be helpful for center specific assessment of risk of graft failure in non HCV patients and discussion regarding relevant morbidity in selected subsets. LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age>60 years, ventilator status, diabetes, hemodialysis and creatinine>1.5mg/dL) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics further leads to lower survival.

Trotter, J. F. (2018). “The diminishing role of liver biopsy in live donor liver transplant.” Liver Transpl. Feb 21. [Epub ahead of print].

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Persistent concerns about donor safety are reflected in the low level of activity in living donor liver transplantation (LDLT) in the United States, currently accounting for 4% of all liver transplants. One of the most important considerations in donor evaluation is the estimation of hepatic steatosis. In fact, most, but not all, centers disqualify live donor candidates with > 10% hepatic steatosis based primarily on donor safety as well as recipient outcomes. Donors with even mild hepatic steatosis (up to 10%) are more likely to have postoperative jaundice, which is evidence of impaired function of the remnant liver. While steatosis is associated with worse initial recipient graft function, the degree of steatosis placing the recipient at risk (> 0 %) is rarely a consideration for LDLT recipients. Hepatic steatosis is becoming more common due to the worldwide increase in obesity. Obesity is the most common indication to disqualify donor candidates early in the evaluation, in part, because of the increased likelihood of hepatitis steatosis as well as associated medical comorbidities. For remaining potential donors, accurate estimation of hepatic steatosis is critical. Fortunately, noninvasive imaging techniques (computed tomographic and magnetic resonance imaging [MRI]) have evolved since the introduction of LDLT more than 20 years ago. At that time, noninvasive imaging provided only a rough estimate of hepatic steatosis, which is insufficient to forego liver biopsy in many instances. Consequently, in this early era of LDLT, some centers elected to biopsy all donor candidates while other centers biopsied a smaller fraction. With more experience, it became apparent that protocol liver biopsy was not helpful in most cases and often identified trivial histologic abnormalities that created more confusion than clarity. Therefore, most centers (60%) follow a “reflexive” biopsy practice, i.e., liver biopsy is performed in selected candidates triggered by a specific abnormality, such as mild biochemical dysfunction or steatosis on magnetic resonance imaging (MRI). Recent advances have diminished reliance on liver biopsy in hepatology. These include ultrasound (US)-based and MRI-based hepatic elastography . For example, at our center, the number of liver biopsies has decreased 90 % in the past 10 years, due in large part to reliance on US-based elastography. Parenthetically, the decrease in performance of liver biopsies by hepatologists, even at busy centers, has resulted in trainees not acquiring sufficient experience in this procedure. Furthermore, advances in MRI techniques for estimating hepatic steatosis have become more sensitive and specific. In fact, the MR spectroscopy proton density fat fraction (MRS-PDFF) is accepted as a valid end point in clinical trials of new therapy for nonalcoholic fatty liver disease. (Excerpt from text, p. 1-3, advance text; no abstract available.)

Kasiske, B. L., S. K. Asrani, M. A. Dew, M. L. Henderson, C. Henrich, A. Humar, A. K. Israni, K. L. Lentine, A. J. Matas, K. A. Newell, D. LaPointe Rudow, A. B. Massie, J. J. Snyder, S. J. Taler, J. F. Trotter and A. D. Waterman (2017). “The living donor collective: A scientific registry for living donors.” Am J Transplant 17(12): 3040-3048.

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In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.

Gonzalez, S. A. and J. F. Trotter (2017). “The rise of the opioid epidemic and hepatitis c positive organs: A new era in liver transplantation.” Hepatology: 2017 Oct [Epub ahead of print].

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The use of hepatitis C virus (HCV) positive organs in liver transplantation has increased in the era of direct-acting antiviral therapy. A rising demand for organs, the 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 US has resulted in a surge of injection drug use, transmission of HCV, and opioid-related overdose deaths. Geographic 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 liver transplants in the US from donors who are HCV positive has increased nearly two-fold within the last three years. The prospect of expanding the organ donor pool with HCV positive donors and achieving acceptable post-transplant 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 post-transplant outcomes in this setting.

Trotter, J. F. (2017). “Pro: Direct-acting agents are associated with occurrence and recurrence of hepatocellular carcinoma.” Liver Transpl: 2017 Oct [Epub ahead of print].

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The advent of direct-acting oral agents (DAA’s) for the treatment of hepatitis C (HCV) is perhaps the most important therapeutic development in the modern practice of hepatology. These drugs cure HCV, the most common indication for liver transplantation. Their efficacy approaches 100 %, requiring as little as 8 weeks of therapy without clinically relevant side effects. Consequently, HCV can be eradicated in almost any treated patient, even those with decompensation, albeit at a slightly lower rate. Clinicians have enthusiastically treated large numbers of infected patients including those with advanced fibrosis to ultimately prevent longterm complications including hepatocellular carcinoma (HCC) and hepatic decompensation either of which may lead to transplantation or death.