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

Natarajan Y, Kramer JR, Yu X, Li L, Thrift AP, El-Serag HB, Kanwal F. Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes. Hepatology (Baltimore, Md.). 2020 Oct 1; 72(4):1242-1252.

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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.

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