Measuring Liver Disease Through the Eyes?
A new collaboration with Dr. Philip Okafor and Dr. Katherine Wong of Stanford Medicine has brought an exciting development to light: signs of liver disease are measurable using eye movements. The project began with an organic discussion about an unmet need in hepatology to detect and measure signs of hepatic encephalopathy, brain pathology associated with liver disease.
The term encephalopathy (εγκέφαλος + πάθος; brain + to suffer) describes a number of brain maladies which can arise from a variety of mechanisms. Some encephalopathies are metabolic, in that the brain suffers from a lack of particular nutrient (e.g., vitamin B in Wernicke’s encephalopathy) or from an imbalance in blood chemistry (e.g., hypoglycemia, hyperglycemia, water or electrolyte metabolism). A second type arises from brain trauma; chronic traumatic encephalopathy (CTE) can result from repeated brain injuries. A third type of encephalopathy can arise due to prion proteins, known as Creutzfeldt-Jakob disease in its human form and Mad Cow in its bovine counterpart. Last, toxic encephalopathy occurs when toxins in the brain lead to deterioration of function; hepatic (ἧπαρ; liver) encephalopathy (HE) arises when the liver fails to filter out toxins that accumulate in the brain.
In the U.S. alone, liver cirrhosis (κιρρός + -ωσις; orange-tawny + state of being) affects an estimated 5.5 million adults, arising when scar tissue replaces healthy liver tissue following drug toxicity (alcoholism, Tylenol), viruses (hepatitis B & C), and non-alcoholic fatty liver disease. In cirrhotic patients, a transition between disease states is marked by the onset of one of four types of liver decompensation, hepatic encephalopathy being one of the four. Whereas all signs of decompensation indicate the progression of liver disease and the associated risk of falls, hospitalization, and mortality, quantitative methods to monitor brain function may detect earlier signs of the development of liver disease.
In patients with liver disease, the presence of hepatic encephalopathy can be difficult to detect and its severity difficult to quantify using psychometric methods. Standard techniques to detect HE involve a series of paper-and-pencil tests (e.g., line tracing, connect the dots, decoding symbols), combined into a composite called the Psychometric Hepatic Encephalopathy Score (PHES). The first experiment in this collaboration used neuroFit ONE to measure aspects of eye-movement performance on a standardized visual tracking task. As shown in the summary graphs below, the normal subject shows behavior consistent with reference populations, whereas the subject with decompensated liver disease shows relative impairments in several metrics, similar to effects observed in civilian and veteran populations with traumatic brain injury. Dr. Okafor presented initial results at the Stanford University Division of Gastroenterology and Hepatology research retreat in November 2017.
Control subject shows metrics of dynamic vision similar to those observed in reference populations.
Patient with decompensated liver disease shows impairment along all dimensions of oculomotor behavior.
