Elevation of Alanine Amino-Transferase Blood Activity Within Normal Values, is Associated with Negative Clinical Outcomes in Anorexia Nervosa Patients. A Retrospective Analysis of 907 Patients

In the human body, the liver acts as a chemical processing plant, filtering blood and managing energy. When liver cells are damaged or stressed, they leak a specific enzyme called alanine aminotransferase, or ALT, into the bloodstream. Doctors have long used the level of this enzyme as a signal: if the amount is high, it usually means the liver is injured. Conversely, if the amount is very low, it can sometimes indicate that the body has lost muscle mass or is in a state of frailty, as muscle tissue also produces this enzyme. For most people, having an ALT level that falls within the standard "normal" range is considered a sign of good health. However, the meaning of these normal numbers can shift dramatically depending on the patient's overall condition.

This complexity becomes critical when looking at patients with anorexia nervosa, a severe eating disorder characterized by extreme weight loss and malnutrition. These individuals often suffer from a dual threat: their bodies may be wasting away muscle, which typically lowers enzyme levels, while their livers may be struggling under the stress of starvation or the shock of eating again, which can raise enzyme levels. For years, medical experts have debated which of these forces wins out in the blood tests of these patients. Does a low-normal enzyme level signal a body that is too weak to recover, or does a high-normal level point to a liver that is actively failing? A new study involving nearly nine hundred patients has provided a surprising answer that challenges previous assumptions about how to read these vital signs.

Researchers at Sheba Medical Center in Israel conducted a detailed review of medical records from 907 women who had been hospitalized for anorexia nervosa between 2013 and 2023. They focused specifically on the very first blood test taken when each patient arrived at the psychiatric ward. To ensure their findings were not clouded by other liver diseases, the team excluded any patient whose enzyme levels were clearly above the normal range, leaving them with a group of patients whose results were technically "normal." The researchers then split this group into two categories based on where their numbers fell within that normal range. One group had lower-normal levels, while the other had higher-normal levels, though both sets of numbers were considered safe by standard medical definitions.

The results of this analysis revealed a stark difference in outcomes between the two groups. Patients with the higher-normal enzyme levels faced significantly worse clinical fates than those with lower levels. The group with higher numbers stayed in the hospital longer, with a median stay of 65 days compared to 56 days for the lower group. More critically, the risk of death was much higher for those with the higher enzyme readings. Over the course of the study, 5.7 percent of the patients in the higher-normal group died, compared to only 2.1 percent of those in the lower-normal group. Even after the researchers accounted for other factors that could influence survival, such as age, body mass index, and the presence of other mental health conditions, the higher enzyme level remained a strong, independent predictor of death.

This finding turns the usual medical logic on its head. In many other populations, including the elderly or those with chronic illnesses, low enzyme levels are often a warning sign of frailty and muscle loss, suggesting a body that is running out of resources. One might expect that in anorexia, where muscle wasting is a defining feature, the lowest numbers would signal the greatest danger. Instead, the data showed that in this specific population, the higher numbers within the normal range were the true danger signal. The researchers suggest that for patients with anorexia, the source of the enzyme in the blood may shift. Because their muscle mass is already so depleted, the enzyme levels are no longer driven by muscle health. Instead, even a slight elevation likely reflects ongoing damage to the liver cells themselves, caused by the intense stress of starvation or the metabolic shock of refeeding.

The study also highlighted that the patients with higher enzyme levels had other distinct characteristics. They tended to have slightly higher levels of albumin, a protein made by the liver, and higher levels of creatine phosphokinase, an enzyme found in muscle. These details suggest that the elevated ALT was not simply a sign of general body breakdown, but rather a specific marker of liver stress occurring even while other parts of the body's chemistry appeared relatively stable. The researchers noted that the frequency of patients being readmitted to the hospital was also a powerful predictor of mortality, reinforcing the idea that the severity of the disease is often measured by how often the body fails to stabilize.

Ultimately, this research suggests that for doctors treating anorexia nervosa, a "normal" blood test result requires a more nuanced interpretation. A value that sits at the top end of the normal range should not be dismissed as benign. Instead, it may indicate a patient whose liver is struggling to cope with the demands of recovery or the ravages of starvation. The study concludes that these higher-normal levels serve as a warning sign of subclinical liver injury, identifying a group of patients who are at greater risk of dying and who may need closer monitoring and more careful management of their nutritional rehabilitation. By recognizing this hidden signal within the standard numbers, medical teams may be better equipped to protect the most vulnerable patients during their most critical moments of recovery.