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Insulin resistance in patients with HBV linked to increase risk for HCC

A retrospective study revealed an association between insulin resistance assessed by homeostasis model assessment index, or HOMA2-IR, and an increased risk for hepatocellular carcinoma in patients with chronic hepatitis B.

“Although chronic HBV infection can lead to the development of HCC, risk of developing HCC is variable among individuals. Hence, identifying risk factors for HCC help define at risk population who may benefit from targeted screening or intervention to prevent HCC,” the researchers wrote. “Among these risk factors, metabolic syndrome is a potentially modifiable risk factor with therapeutic implication. Obesity and diabetes are components of metabolic syndrome, with insulin resistance (IR) as a common pathophysiological mechanism.”

The researchers gathered data from January 2005 to December 2013 on 1,696 HBsAg-positive patients who had serum blood testing that included serum insulin and C-peptide measurement. They estimated insulin resistance by calculating HOMA2-IR with the computer-based solution of the model from the Diabetes Trial Unit at Oxford Center for Diabetes, Endocrinology and Metabolism.

Twenty-four patients developed HCC over a median 5 years (range, 1-10.5 years) and the median HOMA2-IR index score was 1.225 (range, 0.410-5.348). Compared with the rest of the cohort, the patients who developed HCC had higher BMI (25.3 vs. 23.8 kg/m²; P = .003), aspartate aminotransferase (36 vs. 24 U/L; P < .001), alanine aminotransferase (31 vs. 23 U/L; P < .004) and HOMA2-IR score (1.448 vs. 1.217; P = .023), a lower platelet count (165 vs. 212 10³/mm³; P < .001), and were more likely to have hypertension (41.7% vs. 24.2%; P = .048), cirrhosis (29.2% vs. 2.5%; P < .001) and elevated HBV DNA levels (37.5% vs. 18.5%; P = .018).

Compared with patients with lower HOMA2-IR scores, patients with HOMA2-IR scores greater than 1.2 were older (50.9 vs. 50 years; P = .018), more often men (614 vs. 350; P < .001), had higher BMI (25.1 vs. 22.5 kg/m²; P < .001), AST (25 vs. 23 U/L; P < .001), ALT (26 vs. 20 U/L; P < .001) and platelet counts (215 vs. 207 10³/mm³; P = .001), and were more likely to have hypertension (31.8% vs. 16.6%; P < .001), diabetes (12% vs. 2.5%; P < .001) and metabolic syndrome (26% vs. 1.7%; P < .001).

HOMA2-IR was a significant factor for the occurrence of HCC in patients with HBV before adjustment (HR = 2.82; P = .032) and after adjusting for age, sex, cirrhosis and HBV DNA levels (HR = 3.25; P = .028). After dividing HOMA2-IR scores into four quartiles, the researchers found that patients in the highest quartile had a significantly increased risk for HCC compared with those in the lowest quartile both before adjustment (HR = 8.77; P .039) and after the adjusted multivariable model (HR = 9.37; P = .048).

“Our finding suggests that [insulin resistance] in chronic HBV-infected patients can contribute to or accelerate hepatocarcinogenesis,” the researchers concluded. “HOMA2-IR index might be a good surrogate marker for HCC risk assessment in patients with chronic hepatitis B, especially for those without metabolic abnormalities, which warrants further validation.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.