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  The Liver Meeting
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Washington on 04-08
November 2022
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Higher Fibrosis Progression Rate
in NAFLD Group With vs Without Diabetes

  AASLD-The Liver Meeting, November 4-8, 2022, Washington, DC
Mark Mascolini
People with nonalcoholic fatty liver disease (NAFLD) and diabetes ran almost a 75% higher risk of liver fibrosis progression by at least 1 stage than NAFLD patients without diabetes, according to results of a 447-person US analysis [1]. A team working with the NASH Clinical Research Network (CRN) believes their findings suggest people with NAFLD and diabetes may need more frequent monitoring for NAFLD progression.
Researchers estimate that among people over 50 years old with diabetes, about 1 in 7 has NAFLD with advanced fibrosis. Much work shows fibrosis stage strongly determines outcomes in people with NAFLD. In people with nonalcoholic steatohepatitis (NASH)-fatty liver with liver cell damage-fibrosis climbs about 1 stage higher every 7 years. But how fast fibrosis worsens in people with NAFLD and diabetes remains unknown.
To address this question the NASH CRN group ran a multicenter, multiethnic, prospective cohort study, comparing rates of fibrosis progression and regression in people with NAFLD, with or without type 2 diabetes at baseline. To compare progression and regression rates between people with versus without diabetes at baseline, the researchers used linear regression adjusted for age, gender, ethnicity or race, body mass index (BMI), and baseline fibrosis stage. They used a Cox proportional hazards model adjusted for age, gender, BMI, Hispanic ethnicity, and baseline fibrosis stage to estimate hazard ratios for fibrosis progression and regression.
The study took place at eight sites across the United States and enrolled people at least 18 years old with biopsy-proved NAFLD. Everyone had labs and physical measures within 6 months of their biopsy and had a second liver biopsy more than 1 year after their first. Biopsies were centrally read by a pathology committee "in a rigorous systematic manner." The study excluded people in the treatment arm of a clinical trial, transplant recipients, and people with type 1 diabetes, hepatocellular carcinoma, or a liver disease other than NAFLD.
The study group included 447 people, 239 without diabetes at baseline and 208 with baseline type 2 diabetes. People with diabetes were older (average 53.0 vs 49.1, P < 0.001), had a higher proportion of women (70% vs 58%, P = 0.006), a higher average BMI (35.6 vs 33.9 kg/m2, P = 0.005), a higher proportion with metabolic syndrome (74% vs 61%, P = 0.006), a higher fibrosis stage (2.0 vs 1.4, P < 0.001), higher FIB-4 (median 1.3 vs 1.1, P = 0.03), and a higher proportion with borderline or definite NASH (79% vs 57%, P < 0.001).
Median time between biopsies was 3.3 years. Of the 447 cohort members, 151 (34%) had fibrosis progression, 102 (23%) had regression, and 194 (43%) had no change. A significantly higher proportion with than without baseline diabetes progressed to advanced fibrosis (26.0% vs 14.1%, P = 0.008). The whole cohort had an average progression rate of +0.15 stage per year, which works out to an average progression of 1 stage through 6.7 years for these adults with NAFLD. After the statistical adjustments listed above, people with baseline diabetes advanced +0.17 stage per year, whereas people without baseline diabetes advanced +0.13 stage per year, a significant difference (P = 0.02). Those rates mean people with baseline diabetes would progress 1 stage over 5.9 years versus 1 stage over 7.7 years in people without diabetes at baseline.
The proportional hazards model adjusted for age, gender, BMI, Hispanic ethnicity, and baseline fibrosis stage found type 2 diabetes an independent predictor of fibrosis progression in adults with NAFLD (hazard ratio [HR] 1.69, 95% confidence interval [CI]) 1.17 TO 2.43, P = 0.005). Fibrosis would progress almost 1 stage over 12 years in people with NAFLD and baseline diabetes versus three quarters of a stage over 12 years in those without diabetes (+0.93 vs +0.76). After adjustments for the same variables, HbA1c (the diabetes measure) above versus below 7.0% did not predict fibrosis progression.
In an analysis excluding incident (newly diagnosed) diabetes during the study period, people with baseline diabetes ran a 73% higher risk of progressing at least 1 stage than people without baseline diabetes (adjusted HR 1.73, 95% CI 1.13 to 2.65, P = 0.01).
Overall fibrosis regression rate in this whole group with NAFLD stood at -0.13 stage per year to yield an average regression of 1 stage over 7.7 years. Regression rates proved similar in people with and without baseline type 2 diabetes: -0.13 and -0.14 stage per year, or 1 stage over 7.7 years in people with baseline diabetes and 1 stage over 7.1 years in those without diabetes.
On the basis of these results, the NASH CRN team proposed "patients with NAFLD and diabetes may require more frequent monitoring for disease progression" than NAFLD patients without diabetes.
1. Huang D, Wilson LA, Behling C, et al. Fibrosis progression rate among diabetic versus non-diabetic patients with biopsy-proven nonalcoholic fatty liver disease: a multicenter prospective study. AASLD-The Liver Meeting, November 4-8, 2022, Washington, DC. Abstract 10.