Cumulative incidence rate for serious infection in NAFLD nears 50% over 20 years
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Key takeaways:
- Over a median follow-up of 14.1 years, patients with NAFLD had a 71% increased relative risk for being hospitalized with an infection.
- Risk for infection increased with worsening severity of NAFLD histology.
Patients with nonalcoholic fatty liver disease had a significantly greater risk for severe infection requiring hospitalization vs. the general population, with an absolute risk difference of more than 17%at 20 years after diagnosis.
“NAFLD is the most common chronic liver disease, affecting approximately one-quarter of all adults worldwide, but despite its high prevalence, we still have a very limited understanding of its impact on an individual’s long-term health,” Fahim Ebrahimi, MD, MSc, of the department of medical epidemiology and biostatistics at Karolinska Institute, told Healio. “Accumulating evidence suggests that NAFLD can affect multiple organ systems, which is not surprising as the liver has various functions, regulating metabolism and being a central organ of the immune system.”
He continued: “We were intrigued by experimental studies showing that in NAFLD many key immune cells in the liver become dysfunctional at various levels, which may affect disease development and progression, but at the same time also increase the susceptibility to various viral, bacterial and fungal infections.”
In a population-based cohort study published in Clinical Gastroenterology and Hepatology, Ebrahimi and colleagues analyzed data from 12,133 adults with biopsy-proven NAFLD (mean age, 54 years; 54.8% men) from 1969 to 2017 using the Epidemiology Strengthened by histopathology Reports in Sweden (ESPRESSO) cohort. Patients were matched with 57,516 controls without NAFLD from the general population.
Among individuals with NAFLD, 67.8% had simple steatosis, 15.2% had nonalcoholic steatohepatitis with noncirrhotic fibrosis, 11.4% had NASH without fibrosis and 5.6% had cirrhosis.
The primary endpoint was incident severe infection requiring hospitalization, while secondary outcomes included specific infection subgroups, such as sepsis and respiratory tract, gastrointestinal and urogenital infections.
Results showed that over a median follow-up of 14.1 years, 37.2% patients with NAFLD and 26.2% matched controls were hospitalized with a severe infection.
“We found that individuals with NAFLD had a 71% increased relative risk of being hospitalized with an infection,” Ebrahimi said.
Researchers also reported that patients with NAFLD had a higher incidence of severe infection vs. controls (32.3 per 1,000 person-years vs. 17 per 1,000 person-years), the most frequent of which were respiratory (13.8 per 1,000 person-years) and urinary tract infections (11.4 per 1,000 person-years).
The 20-year cumulative incidence rate was 45% vs. 27.8%, respectively, with an absolute risk difference of 17.3% (95% CI, 16.8-17.7) — the equivalent of one extra severe incident infection among every six patients with NAFLD.
“That estimate is indeed quite high,” Ebrahimi said, “and we did not expect that.”
Results also showed the risk for severe infection increased with each stage of histologic severity for simple steatosis (adjusted HR = 1.64; 95% CI, 1.55-1.73), NASH without fibrosis (aHR = 1.84; 95% CI, 1.6-2.12), noncirrhotic fibrosis (aHR = 1.77; 95% CI, 1.56-2) and cirrhosis (aHR = 2.32; 95% CI, 1.92-2.82).
When researchers compared NAFLD patients with their full siblings, the increased risk for severe infections remained (aHR = 1.54; 95% CI, 1.4-1.7).
“Our findings identifying NAFLD patients at risk for severe infections have several clinical implications: Clinicians caring for patients with NAFLD need to be aware of the increased risk for infection and should exercise increased clinical vigilance and consider preventive measures, such as regular review of vaccination status, including pneumococcal, influenza and herpes zoster vaccines and others,” Ebrahimi said. “In addition, known modifiable risk factors such as diabetes mellitus need to be well controlled.”
He added, “These data should also motivate us to better identify individuals with NAFLD and to streamline the care of these individuals to detect and treat infections earlier and reduce associated hospitalizations and infection related mortality.”
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