Newly Defined Liver Disorder Associated With COVID Mortality

Laird Harrison

May 03, 2022

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People with metabolic dysfunction–associated fatty liver disease (MAFLD) ― a newly defined condition ― may be more likely to die from COVID-19, researchers say.

A cohort of people hospitalized for COVID-19 in Central Military Hospital, Mexico City, who met the criteria for MAFLD died at a higher rate than a control group without fatty liver disease, said Martín Uriel Vázquez-Medina, MSc, a researcher in the National Polytechnic Institute in Mexico City.

Patients who met only the criteria for the traditional classification, nonalcoholic fatty liver disease (NAFLD), also died of COVID-19 at a higher rate than the control group, but the difference was not statistically significant.

"It is important to screen for MAFLD," Vázquez-Medina told Medscape Medical News. "It's a new definition, but it has really helped us to identify which patients are going to get worse by COVID-19."

The study was published April 19 in Hepatology Communications.

More Evidence for Clinical Relevance of MAFLD

The finding lends support to an initiative to use MAFLD instead of NAFLD to identify patients whose liver steatosis poses a threat to their health, Vázquez-Medina said.

NAFLD affects as much as a quarter of the world's population. No drugs have been approved to treat it. Some researchers have reasoned that the imprecision of the definition of NAFLD could be one reason for the lack of progress in treatment.

"NAFLD is something that doesn't have positive criteria to be diagnosed," said Vázquez-Medina. "You only say NAFLD when you don't find hepatitis or another disease."

In a 2020 article published in Gastroenterology, an international consensus panel proposed MAFLD as an alternative, arguing that a focus on metabolic dysfunction could more accurately reflect the pathogenesis of the disease and help stratify patients.

Previous research has suggested that patients with MAFLD have a higher risk of atherosclerotic cardiovascular disease and that the prevalence of colorectal adenomas is a higher in these patients compared to patients with NAFLD.

The high prevalence of MAFLD in Mexico — about 30% — could help explain the country's high rate of mortality from COVID-19, Vázquez-Medina said. Almost 6% of people diagnosed with COVID in Mexico have died from it, according to the Johns Hopkins University and Medical Center Coronavirus Resource Center.

Sorting COVID Outcomes by Liver Steatosis

To understand the interaction of MAFLD, NAFLD, liver fibrosis, and COVID-19, Vázquez-Medina and his colleagues analyzed the records of all patients admitted to the Central Military Hospital with COVID-19 from April 4, 2020, to June 24, 2020.

They excluded patients for whom complete data were lacking or liver function test were not conducted in the first 24 hours of hospitalization. Also excluded were patients with significant consumption of alcohol (>30 g/day for men and >20 g/day for women) and those with a history of autoimmune liver disease, liver cancer, decompensated cirrhosis, platelet disorders, or myopathies.

The remaining patients were divided into three groups — 220 who met the criteria for MAFLD, 79 who met the criteria for NAFLD but not MAFLD, and 60 other patients as a control group.

The researchers defined MAFLD as the presence of liver steatosis detected with a noninvasive method and one of the following: overweight (body mass index [BMI], 25–29.9 kg/m2), type 2 diabetes, or the presence of two metabolic abnormalities (blood pressure >140/90 mm Hg, plasma triglycerides >150 mg/dL, plasma high-density lipoprotein cholesterol <40 mg/dL in men and <50 mg/dL in women, and prediabetes).

They defined NAFLD as the presence of liver steatosis without the other criteria for MAFLD.

The patients with MAFLD were the most likely to be intubated and were the most likely to die, followed by those with NAFLD and those in the control group.

Table. Mortality and Intubation Rates Compared

  MAFLD, n = 220 NAFLD, n = 79 Control, n = 60
Mortality, % 55.00 51.90 38.33
Intubation, % 44.09 40.51 20.00


The difference in mortality between the MAFLD group and the control group was statistically significant (P = .02). The mortality difference between the NAFLD and the control group fell just short of statistical significance (P = .07).

For intubation, the difference between the MAFLD and the control group was highly statistically significant (P = .001), and the difference between the NAFLD and the control group was also statistically significant (P = .01)

Patients with advanced fibrosis and either MAFLD or NAFLD were also more likely to die than patients in the control group with advanced fibrosis.

That's why screening for MAFLD is important, Vázquez-Medina said.

Next Steps and New Questions

Future research should examine whether patients with MAFLD have elevated levels of biomarkers for inflammation, such as interleukin 6, Vázquez-Medina said. A "chronic low proinflammatory state" may be the key to understanding the vulnerability of patients to MAFLD to COVID-19, he speculated.

The metabolic traits associated with MAFLD could explain the higher mortality and intubation rates with COVID, said Rohit Loomba, MD, MHSc, a professor of medicine in the Division of Gastroenterology at the University of California, San Diego, who was not involved in the study.

"Hypertension, diabetes, and obesity increase the risk of complications from COVID in all patients, whether they have been diagnosed with NAFLD or not," he told Medscape Medical News in an email.

Vasquez-Medina pointed out that the patients with MAFLD had a higher risk of mortality even after adjusting for age, sex, type 2 diabetes, hypertension, overweight, and obesity (BMI ≥30 kg/m2). MAFLD also was more strongly associated with a poor outcome than either hypertension alone or obesity alone. Only age emerged as a significant independent covariate in the study.

Loomba also questioned whether the regression model used in this study for liver steatosis was "fully reflective of NAFLD."

The researchers identified liver steatosis with a diagnostic formula that used noninvasive clinical (BMI) and laboratory tests (alanine aminotransferase), citing a study that found the regression formula was better at diagnosing NAFLD than FibroScan.

Vázquez-Medina reported no relevant financial relationships. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc, Madrigal, Metacrine, Inc, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals, and Viking Therapeutics. He is co-founder of LipoNexus.

Hep Comm. Published online April 19, 2022. Full text

Laird Harrison writes about science, health, and culture. His work has appeared in magazines, newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at or follow him on Twitter: @LairdH.

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