Long-term follow-up of patients with NAFLD and elevated liver enzymes

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsyproven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P ‫؍‬ .01). These subjects more often died from cardiovascular (P ‫؍‬ .04) and liver-related (P ‫؍‬ .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P ‫؍‬ .02), they were more insulin resistant (P ‫؍‬ .04), and they exhibited more pronounced hepatic fatty infiltration (P ‫؍‬ .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain. (HEPATOLOGY 2006;44:865-873.)

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

“…Our findings showed more patients developed end‐stage liver disease compared to what has been reported (1.2%‐5.4%) 7, 8, 13, 33. Angulo et al13 showed 4.2% of all patients developed end‐stage liver disease.…”

“…During follow‐up, 8 patients were reclassified as alcoholic fatty liver disease, and therefore the final cohort constituted of 129 patients with NAFLD. A previous follow‐up study of this cohort (first follow‐up) was conducted between 2003 and 2005 (details of data collection and results have been reported elsewhere8). The current follow‐up (second follow‐up) was conducted between 2013 and 2015.…”

“…Some patients with NAFLD develop progressive fibrosis and subsequent cirrhosis with an increased risk of hepatocellular carcinoma 6. The prevalence of cirrhosis among patients with NAFLD is approximately 5%, and patients with NAFLD have an increased mortality compared to control populations 7, 8, 9. Today, NAFLD is the second leading etiology among adult patients awaiting liver transplant in the United States 10…”

“…There are few paired biopsy studies with approximately 520 patients in total,7, 8, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and all but two studies have a median follow‐up time of less than 7 years (range, 3.0‐7.0 years). Albeit, some studies only include patients with NASH, the rate of fibrosis progression does not seem to be affected by the presence of steatohepatitis.…”

“…NAFLD is a slowly progressive disease,11 and most follow‐up studies have too short a follow‐up time to assess fibrosis progression 24. Fibrosis progression is seen in 27%‐52% of patients7, 8, 19, 21, 22, 24 over a mean of 3.0‐13.8 years of follow‐up, with the majority of patients with NAFLD having static or regressive fibrosis. Baseline variables predicting fibrosis progression have been hard to determine.…”