From the Journals

Long COVID associated with risk of metabolic liver disease



Postacute COVID syndrome (PACS), an ongoing inflammatory state following infection with SARS-CoV-2, is associated with greater risk of metabolic-associated fatty liver disease (MAFLD), according to an analysis of patients at a single clinic in Canada published in Open Forum Infectious Diseases.

MAFLD, also known as nonalcoholic fatty liver disease (NAFLD), is considered an indicator of general health and is in turn linked to greater risk of cardiovascular complications and mortality. It may be a multisystem disorder with various underlying causes.

PACS includes symptoms that affect various organ systems, with neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, psychological, sensory, and dermatologic clusters. An estimated 50%-80% of COVID-19 patients experience one or more clusters of symptoms 3 months after leaving the hospital.

But liver problems also appear in the acute phase, said Paul Martin, MD, who was asked to comment on the study. “Up to about half the patients during the acute illness may have elevated liver tests, but there seems to be a subset of patients in whom the abnormality persists. And then there are some reports in the literature of patients developing injury to their bile ducts in the liver over the long term, apparently as a consequence of COVID infection. What this paper suggests is that there may be some metabolic derangements associated with COVID infection, which in turn can accentuate or possibly cause fatty liver,” said Dr. Martin in an interview. He is chief of digestive health and liver diseases and a professor of medicine at the University of Miami.

“It highlights the need to get vaccinated against COVID and to take appropriate precautions because contracting the infection may lead to all sorts of consequences quite apart from having a respiratory illness,” said Dr. Martin.

The researchers retrospectively identified 235 patients hospitalized with COVID-19 between July 2020 and April 2021. Overall, 69% were men, and the median age was 61 years; 19.2% underwent mechanical ventilation and the mean duration of hospitalization was 11.7 days. They were seen for PACS symptoms a median 143 days after COVID-19 symptoms began, with 77.5% having symptoms of at least one PACS cluster. Of these clusters, 34.9% were neurocognitive, 53.2% were respiratory, 26.4% were musculoskeletal, 29.4% were psychological, 25.1% were dermatologic, and 17.5% were sensory.

At the later clinical visit for PACS symptoms, all patients underwent screening for MAFLD, which was defined as the presence of liver steatosis plus overweight/obesity or type 2 diabetes. Hepatic steatosis was determined from controlled attenuation parameter using transient elastrography. The analysis excluded patients with significant alcohol intake or hepatitis B or C. All patients with liver steatosis also had MAFLD, and this included 55.3% of the study population.

The hospital was able to obtain hepatic steatosis index (HSI) scores for 103 of 235 patients. Of these, 50% had MAFLD on admission for acute COVID-19, and 48.1% had MAFLD upon discharge based on this criterion. At the PACS follow-up visit, 71.3% were diagnosed with MAFLD. There was no statistically significant difference in the use of glucocorticoids or tocilizumab during hospitalization between those with and without MAFLD, and remdesivir use was insignificant in the patient population.

Given that the prevalence of MAFLD among the study population is more than double that in the general population, the authors suggest that MAFLD may be a new PACS cluster phenotype that could lead to long-term metabolic and cardiovascular complications. A potential explanation is loss of lean body mass during COVID-19 hospitalization followed by liver fat accumulation during recovery.

Other infections have also shown an association with increased MAFLD incidence, including HIV, Heliobacter pylori, and viral hepatitis. The authors worry that COVID-19 infection could exacerbate underlying conditions to a more severe MAFLD disease state.

The study is limited by a small sample size, limited follow-up, and the lack of a control group. Its retrospective nature leaves it vulnerable to biases.

“The natural history of MAFLD in the context of PACS is unknown at this time, and careful follow-up of these patients is needed to understand the clinical implications of this syndrome in the context of long COVID,” the authors wrote. “We speculate that [MAFLD] may be considered as an independent PACS-cluster phenotype, potentially affecting the metabolic and cardiovascular health of patients with PACS.”

One author has relationships with several pharmaceutical companies, but the remaining authors reported no conflicts of interest. Dr. Martin has no relevant financial disclosures.

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