Increased risk of cirrhosis and hepatocellular cancer during long-term follow-up of patients with biopsy-proven NAFLD

Abstract

Objective: Our aims were to investigate the natural history of biopsy-proven non-alcoholic fatty liver disease (NAFLD) in Sweden, its associated complications, the clinical and biochemical factors associated with more advanced liver disease and the survival rate with a mean follow-up time of 27 years.

Material and methods: All subjects participating in the population-based prospective cohort study Malmö Preventive Project (MPP) from 1974 to 1992 who had undergone liver biopsy with the diagnosis of NAFLD were included. The remaining MPP cohort was used as a control group. Subjects with other liver diseases and alcohol overconsumption were excluded. A panel of blood tests was analyzed in the MPP cohort. Follow-up of the NAFLD patients included studies of medical records, pathology records and mortality rates from the Swedish National Board of Health and Welfare's register until the end of 2011.

Results: A total of 36 patients were diagnosed with biopsy-proven NAFLD. Median follow-up time was 27.0 years (6.32-35.3). Nine patients (25%) were diagnosed with cirrhosis and five (14%) with hepatocellular cancer, all with a previous diagnosis of cirrhosis. There were significant differences in liver function tests, insulin resistance (as homeostasis model assessment of insulin resistance) and body mass index (BMI) in patients with NAFLD compared with the control group. Mortality in the NAFLD group was significantly higher, 58.3% compared to 33.8% (p = 0.004). Hepatocellular cancer accounted for 23.8% of all deaths in the NAFLD group, compared to 0.7% (p = 0.000).

Conclusions: NAFLD can progress to advanced liver disease, including cirrhosis, with a higher than expected mortality and incidence of hepatocellular cancer.

Keywords: hepatocellular carcinoma; liver cirrhosis; metabolic syndrome; mortality; non-alcoholic fatty liver disease.