Patients with non-alcoholic fatty liver disease (NAFLD) and type 2 Diabetes may be at significantly higher risk of hepatic decompensation and liver cancer, researchers reported.

In a meta-analysis of six studies that included 1,737 patients with NAFLD followed for approximately 3 years, those with diabetes had twice the risk for developing hepatic decompensation (HR 2.15, 95% CI 1.39-3.34) compared with those without diabetes, Rohit Loomba, MD, of the University of California San Diego School of Medicine in La Jolla, and colleagues reported in The Lancet Gastroenterology and Hepatology.

The patients with NAFLD and type 2 diabetes were also more than five times as likely to develop liver cancer (HR 5.34, 95% CI 1.67-17.09), the study found. In both analyses, the researchers adjusted for potential confounders including age, race or ethnicity, BMI, and baseline liver stiffness.

“This meta-analysis of individual participant-level data from participants with NAFLD from six international sites provides high-level evidence that people with type 2 diabetes are at substantially higher risk of hepatic decompensation and hepatocellular carcinoma, compared to people without type 2 diabetes,” Loomba’s team wrote.

“These data highlight the importance of ensuring comparable proportions of participants with type 2 diabetes in the treatment and control groups of clinical trials in NAFLD. These findings indicate the need for a concerted global effort to reduce the morbidity of NAFLD associated with type 2 diabetes,” the researchers said.

The prevalence of type 2 diabetes among patients with NAFLD is approximately 23%, Eduardo Vilar-Gomez, MD, PhD, of the Indiana University School of Medicine, Indianapolis, noted in an editorial accompanying the study.

“Taken together, these findings provide compelling clinical data to indicate that type 2 diabetes is associated with advanced liver disease, faster disease progression, and worse liver-related outcomes in patients with NAFLD,” Vilar-Gomez wrote.

“Notably, individuals with type 2 diabetes with cirrhosis have a high risk of decompensation, hepatocellular carcinoma, and death, suggesting that they should undergo primary risk assessment, be followed more closely, and offered early treatment options such as intensive lifestyle interventions, metabolic surgery, or glucagon-like peptide-1 (GLP-1) agonists to reduce the risk of complications and death,” Vilar-Gomez advised.

Evidence suggests glycemic control is a chief factor in the link between type 2 diabetes and NAFLD outcomes, Vilar-Gomez noted, citing a previous study of patients with NAFLD that found every 1% increase in glycated hemoglobin (HbA1c) was associated with a 15% increased risk for hepatic fibrosis severity.

Loomba and colleagues reported that HbA1c was an independent predictor of hepatic decompensation (HR 1.31, 95% CI 1.10-1.55) after adjusting for age, BMI, and race/ethnicity.

The severity and progression of NAFLD is likely to depend on factors such as glycemic control and the concurrent use of multiple medications to manage comorbid conditions, Vilar-Gomez said.

In the studies analyzed by Loomba’s group, patients underwent liver fibrosis examination by magnetic resonance elastography and were longitudinally assessed for hepatic decompensation and other outcomes. The patients came from the U.S., Japan, and Turkey. Their mean age was 58, approximately half were women, and their mean BMI was 31.

Of the 1,737 patients, 736 had type 2 diabetes. Over the course of the study, 105 patients developed hepatic decompensation and 22 were diagnosed with liver cancer.

Loomba and coauthors noted that study data had been collected at tertiary care centers, which could have introduced selection bias for participants at higher risk for decompensation. The meta-analysis did not include longitudinal HbA1c data or information on the effect of diabetes treatments on liver decompensation. Finally, the follow up time was relatively short, the authors said.

“These data serve as a call to action to prevent type 2 diabetes and reduce the growing burden of NAFLD and NAFLD-related hepatocellular carcinoma,” they nevertheless concluded.