Transplantation for Nonalcoholic Steatohepatitis

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Abstract

I n the United States, the unadjusted survival after liver transplant (LT) in 2011 was 88.2%. 1 This remarkable statistic is more impressive when considering that transplant recipients are globally sicker at the time of LT at the present time, compared with previous eras. In recent years, the recipient age at LT has increased. The proportion of subjects with Model for End-Stage Liver Disease score greater than 15 has also increased and num-ber of candidates withdrawn from the list for being too sick to transplant has increased nearly 3-fold over the last few years; in fact, in 2012 there were just as many people removed from the list as too sick to transplant (12.6%) as those that die on the list (13.1%; http:// optn.transplant.hrsa.gov). There is a concern that wait-list mortality may start rising again. 1 In this dynamic milieu, the characteristics of persons that receive trans-plants has evolved. The frequency of transplantation for nonalcoholic steatohepatitis (NASH)–related cirrhosis and hepatocellular carcinoma has dramatically increased over the last decade. 2 Currently, cirrhosis related to nonal-coholic fatty liver disease (NAFLD) is the third or fourth most common indication for LT in the United States and is expected to increase. A significant increase in the burden related to hepatocellular carcinoma may be in per-sons with NAFLD. 3,4 Before LT, compared to the general population, there is an independent association between NASH and all-cause mortality, incidence of cancer, espe-cially hepatocellular carcinoma, incidence and prevalence of cardiovascular disease, and major complications and death after surgery. 5,6 Given that a critical mass of literature has been amassed on LT for NASH-related cirrhosis over the last decade, and in light of disparate rates of transplantation for NAFLD compared with other etiologies, a review on this subject is welcome. 7 In a systematic review and meta-analysis reported in this issue of the journal, Wang and colleagues 8 examine the global literature on LT for NASH or NAFLD. The patient survival was similar for persons transplanted with NASH compared with other etiologies at 1 year (OR ¼ 0.77, 95% CI ¼ 0.59–1.00), 3 years (OR ¼ 0.97, 95% CI ¼ 0.67–1.40), and 5 years (OR ¼ 1.09, 95% CI 0.77–1.56) after LT. However, sub-jects who received transplants for NASH had more deaths due to cardiovascular events (OR ¼ 1.65, 95% CI ¼ 1.01–2.70) and sepsis (OR ¼ 1.71, 95% CI ¼ 1.17–2.50). Though data on recurrent NASH were not available, graft failure rates were lower among NASH recipients than other etiologies. As expected, the findings were limited by the het-erogeneity of the patient population, practice patterns, and variable definition of NASH used in the various single-center studies. For example, some studies required only the clinical phenotype rather than histo-logic evidence for a patient with cirrhosis to be included as a NASH subject. Some studies included cryptogenic cirrhosis as a NASH-related transplant whereas other studies compared NASH cirrhosis to cryptogenic cirrhosis. Not all studies adjusted for relevant factors such as age, disease severity, and donor characteristics between the NASH and comparison groups. In sensitivity analysis, it was hard to surmise long-term results given the lack of complete follow-up, incomplete ascertainment of events of interest, and missing data. Further, definition of a cardiovascular event (only 1 study provided a defi-nition of a cardiac event as death from any cardiac cause, nonfatal myocardial infarction, new-onset heart failure, cardiac arrest, supraventricular tachycardia requiring intervention, atrial fibrillation or flutter, symptomatic stable ventricular tachycardia requiring treatment, complete heart block, or stroke) used across other studies were unclear. Whether these events were sys-tematically collected or only self-reported are unknown, though likely assumed to be the latter. Infection-related end points were also likely skewed more toward events captured during the initial hospitalization rather than future time points in the posttransplant course. However, the noninferior survival for subjects receiving transplants for NASH compared with the other etiologies has been reported in an analysis of national transplant databases in the United States. 3,4 Almost all of the studies included in the systematic review were pub-lished in the last 4 years. Some robust studies from the past were not included, potentially for not meeting the inclu-sion criteria for the study. However, these prior studies also had a similar message that survival for NASH-related transplant was not lower compared to other etiologies.

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APA

Singal, A. K., & Charlton, M. (2015). Transplantation for Nonalcoholic Steatohepatitis. In Transplantation of the Liver: Third Edition (pp. 250–255). Elsevier Inc. https://doi.org/10.1016/B978-1-4557-0268-8.00022-1

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