Predictors of De Novo Nonalcoholic Fatty Liver Disease After Liver Transplantation and Associated Fibrosis.

Nonalcoholic fatty liver disease (NAFLD) can occur de novo in patients undergoing liver transplantation (LT) for indications other than NAFLD, and it has been increasingly recognized as a complication in the post-LT setting. This study aims to better characterize de novo NAFLD after LT by identifying risk factors for its development, describing incidence and extent of fibrosis, assessing the diagnostic utility of noninvasive serum fibrosis algorithms, and comparing survival to those without NAFLD. This was a retrospective single-center analysis of de novo NAFLD in a post-LT cohort. Those whose primary indication for LT was nonalcoholic steatohepatitis (NASH) were excluded. Risk factors were analyzed by univariate and multivariate analyses. De novo NAFLD and fibrosis were assessed on posttransplant liver biopsies, and noninvasive fibrosis scores were calculated from concomitant blood tests. After applying the exclusion criteria, 430 for-cause post-LT biopsies were evaluated; 33.3% (n = 143) had evidence of de novo steatosis and/or NASH at a median of 3.0 years after transplant. On multivariate analysis, body mass index (BMI; odds ratio [OR], 1.12; P < 0.001), diabetes mellitus (OR, 3.01; P = 0.002), hepatitis C virus (OR, 4.61; P < 0.001), weight gain (OR, 1.03; P = 0.007), and sirolimus use (OR, 3.11; P = 0.02) were predictive of de novo NAFLD after LT. Significant fibrosis (≥F2) was present in almost 40% of the cohort. Noninvasive serum fibrosis scores were not useful diagnostic tests. There was no significant difference in the short-term or longterm survival of patients who developed de novo NAFLD. In conclusion, diabetes, BMI, weight gain after LT, and sirolimus-based immunosuppression, in keeping with insulin resistance, were the only modifiable factors associated with development of de novo NAFLD. A significant proportion of patients with de novo NAFLD had fibrosis and given the limited utility of noninvasive serum fibrosis algorithms, alternative noninvasive tools are required to screen for fibrosis in this population. There was no significant difference in the short-term or longterm survival of patients who developed de novo NAFLD.

Expanding the donor pool: Donation after circulatory death and living liver donation do not compromise the results of liver transplantation.

Because of the shortfall between the number of patients listed for liver transplantation (LT) and the available grafts, strategies to expand the donor pool have been developed. Donation after circulatory death (DCD) and living donor (LD) grafts are not universally used because of the concerns of graft failure, biliary complications, and donor risks. In order to overcome the barriers for the implementation of using all 3 types of grafts, we compared outcomes after LT of DCD, LD, and donation after brain death (DBD) grafts. Patients who received a LD, DCD, or DBD liver graft at the University of Toronto were included. Between January 2009 through April 2017, 1054 patients received a LT at our center. Of these, 77 patients received a DCD graft (DCD group); 271 received a LD graft (LD group); and 706 received a DBD graft (DBD group). Overall biliary complications were higher in the LD group (11.8%) compared with the DCD group (5.2%) and the DBD group (4.8%; P < 0.001). The 1-, 3-, and 5-year graft survival rates were similar between the groups with 88.3%, 83.2%, and 69.2% in the DCD group versus 92.6%, 85.4%, and 84.7% in the LD group versus 90.2%, 84.2%, and 79.9% in the DBD group (P = 0.24). Furthermore, the 1-, 3-, and 5-year patient survival was comparable, with 92.2%, 85.4%, and 71.6% in the DCD group versus 95.2%, 88.8%, and 88.8% in the LD group versus 93.1%, 87.5%, and 83% in the DBD group (P = 0.14). Multivariate Cox regression analysis revealed that the type of graft did not impact graft survival. In conclusion, DCD, LD, and DBD grafts have similar longterm graft survival rates. Increasing the use of LD and DCD grafts may improve access to LT without affecting graft survival rates. Liver Transplantation 24 779-789 2018 AASLD.

Economic costs of childhood stunting to the private sector in low- and middle-income countries.

Background: Stunting during childhood has long-term consequences on human capital, including decreased physical growth, and lower educational attainment, cognition, workforce productivity and wages. Previous research has quantified the costs of stunting to national economies however beyond a few single-country datasets there has been a limited number of which have used diverse datasets and have had a dedicated focus on the private sector, which employs nearly 90% of the workforce in many low- and middle-income countries (LMICs). We aimed to examine (i) the impact of childhood stunting on income loss of private sector workforce in LMICs; (ii) to quantify losses in sales to private firms in LMICs due to childhood stunting; and (iii) to estimate potential gains (benefit-cost ratios) if stunting levels are reduced in select high prevalence countries. Methods: This multiple-methods study engaged multi-disciplinary technical advisers, executed several literature reviews, used innovative statistical methods, and implemented health and labor economic models. We analyzed data from seven longitudinal datasets (up to 30+ years of follow-up; 1982-2016; Peru, Ethiopia, India, Vietnam, Philippines, Tanzania, Brazil), 108 private firm datasets (spanning 2008-2020), and many global datasets including Joint Malnutrition Estimates, and World Development Indicators to produce estimates for 120+ LMICs (with estimates up to 2021). We studied the impact of childhood stunting on adult cognition, education, and height as pathways to wages/productivity in adulthood. We employed cloud-based artificial intelligence (AI) platforms, and conducted comparative analyses using three analytic approaches: traditional frequentist statistics, Bayesian inferential statistics and machine learning. We employed labour and health economic models to estimate wage losses to the private sector worker and firm revenue losses due to stunting. We also estimated benefit-cost ratios for countries investing in nutrition-specific interventions to prevent stunting. Findings: Across 95 LMICs, childhood stunting costs the private sector at least US$135.4 billion in sales annually. Firms from countries in Latin America and the Caribbean and East Asia and Pacific regions had the greatest losses. Totals sales losses to the private sector accumulated to 0.01% to 1.2% of national GDP across countries. Sectors most affected by childhood stunting were manufacturing (non-metallic mineral, fabricated metal, other), garments and food sectors. Sale losses were highest for larger sized private firms. Across regions (representing 123 LMICs), US$700 million (Middle East and North Africa) to US$16.5 billion (East Asia and Pacific) monthly income was lost among private sector workers. Investing in stunting reduction interventions yields gains from US$2 to US$81 per $1 invested annually (or 100% to 8000% across countries). Across sectors, the highest returns were in elementary occupations (US$46) and the lowest were among agricultural workers (US$8). By gender, women incurred a higher income penalty from childhood stunting and earned less than men; due to their relatively higher earnings, the returns for investing in stunting reduction were consistently higher for men across most countries studied. Interpretation: Childhood stunting costs the private sector in LMICs billions of dollars in sales and earnings for the workforce annually. Returns to nutrition interventions show that there is an economic case to be made for investing in childhood nutrition, alongside a moral one for both the public and private sector. This research could be used to motivate strong public-private sector partnerships to invest in childhood undernutrition for benefits in the short and long-term.