Glycerol-3-phosphate Acyltransferase1 Is a Model-Agnostic Node in Nonalcoholic Fatty Liver Disease: Implications for Drug Development and Precision Medicine.

Left untreated nonalcoholic fatty liver disease (NAFLD) can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The observed failure of clinical trials in NASH may suggest that current model systems do not fully recapitulate human disease, and/or hallmark pathological features of NASH may not be driven by the same pathway in every animal model let alone in each patient. Identification of a model-agnostic disease-associated node can spur the development of effective drugs for the treatment of liver disease. Glycerol-3-phosphate acyltransferase1 (GPAT1) plays a pivotal role in lipid accumulation by shunting fats away from oxidation. In the present study, hepatic GPAT1 expression was evaluated in three etiologically different models of NAFLD. Compared to the sham cohort, hepatic GPAT1 mRNA levels were elevated by ∼5-fold in steatosis and NASH with fibrosis with immunofluorescent staining revealing increased GPAT1 in the fatty liver. A significant and direct correlation (r = 0.88) was observed between hepatic GPAT1 mRNA expression and severity of the liver disease. Picrosirius red staining revealed a logarithmic relation between hepatic GPAT1 mRNA expression and scar. These data suggest that hepatic GPAT1 is an early disease-associated model-agnostic node in NAFLD and form the basis for the development of a potentially successful therapeutic against NASH.

The cost of Medicaid coverage for the uninsured: evidence from Buncombe County, North Carolina.

BACKGROUND: The Affordable Care Act gives states the option to expand state Medicaid programs to cover many who are currently uninsured. The potential financial impact has not been thoroughly examined. We characterized the health risk of uninsured adults in Buncombe County, North Carolina, relative to that of local Medicaid recipients, to estimate the cost of expanding Medicaid coverage to include the uninsured. METHODS: We obtained de-identified patient enrollment and claims data for 2008 from the Division of Medical Assistance, North Carolina Department of Health and Human Services and from the 3 safety-net providers who care for most of the county's low-income uninsured adults. We used the Chronic Illness and Disability Payment System (CDPS) risk-adjustment tool to measure the relative health risk of the two populations. Based on actual spending in the Medicaid group and its health risk relative to that of the uninsured, we then projected how much it would have cost to provide Medicaid coverage for these uninsured in 2008. RESULTS: We estimated, based on CDPS adjustment for demographics and diagnoses, that these uninsured adults would have incurred costs 13% greater than those of the actual nondisabled adult Medicaid population. The projected cost of providing Medicaid coverage to these uninsured would have been $4,320 per person. LIMITATIONS: Data were drawn from only the 3 major safety-net organizations and therefore excluded care obtained from other safety-net providers. Also, this sample of uninsured people included some who are ineligible for Medicaid because of their citizenship status. Furthermore, Medicaid enrollment might lead to increased utilization, revealing a greater burden of illness than we detected. CONCLUSION: In Buncombe County, uninsured adults who enroll in expanded Medicaid are likely to have somewhat more costly health problems than do currently enrolled nondisabled adults.

Do free clinics reduce unnecessary emergency department visits? The Virginian experience.

As part of the safety net, free clinics (FCs) increase access to preventive and primary care for the uninsured. This study compared a group of uninsured FC users and a group of uninsured non-FC users to explore the impact of FC enrollment on the pattern of ED visits, as characterized by (1) level of complexity of care received at the ED, and (2) avoidable vs. unavoidable as classified by an existing clinical algorithm. Emergency department visits by FC users were less likely to be low-level-of-care than visits by non-FC users (OR 0.89, 95% CI 0.84-0.93). Free clinic enrollment was not a statistically significant predictor of avoidable visits (p=.6465). We found that the group of individuals who had access to primary care at the local FCs were significantly less likely than the group of uninsured individuals who were not enrolled in a FC to use the ED for care with lower levels of clinical complexity. Thus, the cost of increasing the primary care workforce as the Medicaid population expands may be worth it in the long run. Further exploration into what characterizes an effective FC is needed.