Liver Enzyme Ratio Tied to Higher Mortality Risk in Secondary HLH

Liver Enzyme Ratio Tied to Higher Mortality Risk in Secondary HLH
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The proportions of two liver-associated enzymes found in adults with secondary hemophagocytic lymphohistiocytosis (sHLH) is an indicator of the patients’ mortality risk, a study suggests.

These enzymes, called aspartate transaminase, or AST, and alanine transaminase, or ALT, are usually present in high levels in sHLH patients. Their ratio — AST/ALT — has been suggested as a useful prognostic predictor in other illnesses and malignant cancers.

The study reporting these new findings, titled “The Prognosis Role of AST/ALT (De Ritis) Ratio in Patients with Adult Secondary Hemophagocytic Lymphohistiocytosis,” was published in the journal Mediators of Inflammation.

Liver enlargement and increased levels of liver enzymes often accompany sHLH, and some observational studies have suggested that liver damage, in particular, causes worse outcomes for people with the immune disorder. However, physicians lack good data on how to identify these at-risk patients.

Damaged cells — often of the liver but also of other organs — are known to release higher levels of the two enzymes, AST and ALT. The ratio of AST to ALT is called the De Ritis ratio.

Now, researchers from the First Affiliated Hospital of Nanjing Medical University, in China, hypothesized that the De Ritis ratio could identify higher-risk sHLH patients with liver damage.

To test their hypothesis, the team reviewed clinical data from 289 sHLH patients, ages 18 to 86, with a median age of 53, who were diagnosed at their hospital from September 2014 to December 2019.

In the group analyzed, the median De Ritis ratio level was 1.34, suggesting liver damage.

Individuals with higher De Ritis ratios showed lab findings consistent with clinical parameters for sHLH (disease activity) and overall inflammation. These were reflected in higher levels of hemophagocytes — cells that degrade, or “eat” red blood cells — lactate dehydrogenase, triglycerides, ferritin, and beta-2-microglobulin. Cases of malignancy-associated HLH, known as MHLH, also were found to be associated with higher De Ritis ratios.

In contrast, high De Ritis ratios tended to correlate with low platelet counts, consistent with disease activity and an inflammatory status.

In total, 205 deaths were reported among patients in a median follow-up time of 60 days. Of these, 134 involved MHLH.

The researchers then grouped the patients into thirds, based on the value of their De Ritis ratio.

The two-thirds with lower De Ritis ratios — subgroups who had ferritin levels above 10,000 microgram/mL, soluble interleukin-2 receptor levels of no more than 20,000 nanograms/mL, and those without Epstein-Barr virus infection, with MHLH, and those who had received therapeutic interventions — had comparable survival rates.

By comparison, the third of patients with the highest De Ritis ratios showed a significantly higher risk of mortality. Of note, an individual’s risk of mortality appeared also to correlate significantly with MHLH in those with the highest De Ritis ratios, but not with non-MHLH.

Overall, the results suggested that measuring a patient’s De Ritis ratio is a useful and low-cost way of assessing the individual’s risk of mortality.

Because the one-third of participants in this study with the highest ratios had the worst overall survival outcomes, the researchers believe that this measurement may prove particularly valuable in identifying the highest-risk sHLH patients.

In conclusion, the investigators wrote that “the De Ritis ratio is a strong and independent predictor for overall survival in patients with sHLH.”

“Further studies are warranted,” the team added.

Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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