Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes.

BACKGROUND AND AIMS

The long-term risk of disease for patients with nonalcoholic fatty liver disease (NAFLD) in the absence of elevated enzymes is unclear. We conducted a retrospective cohort study using the Corporate Data Warehouse of the Veterans Health Administration.

APPROACH AND RESULTS

We classified patients into three groups: patients with steatosis/normal alanine aminotransferase (ALT), steatosis/elevated ALT, and no steatosis/normal ALT. We examined incidence rates for cirrhosis and hepatocellular carcinoma (HCC) and conducted cause-specific hazard models to evaluate the risk of cirrhosis and HCC. We identified 3,522 patients with steatosis/normal ALT, 15,419 patients with steatosis/elevated ALT, and 9,267 patients with no steatosis/normal ALT. The mean age in each group was 58.9, 54.7 and 59.3 years, respectively; over 90% were men. Compared to patients with hepatic steatosis/normal ALT, those with steatosis/elevated ALT were younger and more likely to be obese (both P < 0.01). In patients with steatosis/normal ALT, the incidence rates of cirrhosis and HCC were 1.22 (95% confidence interval [CI]: 0.83-1.74) and 0.20 (95% CI: 0.06-0.46) per 1,000 person-years, respectively; this was lower than in patients with steatosis/elevated ALT (cirrhosis: 3.85; 95% CI: 3.50-4.23, and HCC: 0.37; 95% CI: 0.26-0.49). Patients with steatosis/elevated ALT had a higher risk of developing cirrhosis (adjusted hazard ratio: 3.37; 95% CI:  2.34-4.86; P < 0.01) than patients with steatosis/normal ALT; they also had a higher risk of HCC, although it did not reach statistical significance (hazard ratio: 2.07; 95% CI: 0.82-5.28; P = 0.13). The risk of cirrhosis and HCC in patients with steatosis/normal ALT and those without steatosis was not significantly different.

CONCLUSIONS

Patients with hepatic steatosis with persistently normal ALT are at lower risk for cirrhosis compared to those with steatosis and elevated ALT and not different from the risk in a clinical cohort without hepatic steatosis.