These results demonstrate that maintenance of weight reduction and increased physical activity result in a sustained improvement in ALT, fasting insulin levels, and HRQL in overweight patients with chronic liver disease. This sustained improvement was seen both in patients with NAFLD and in those with steatosis in association with another chronic liver disease.
In an earlier study, we demonstrated that in the short term, weight loss reduced hepatic steatosis and fibrosis in patients with chronic HCV.11
In the current study, we demonstrated a similar early histological improvement in an additional small number of patients with obesity related fatty liver disease. Although liver biopsies were not performed at 15 months, it is likely that the sustained improvement in ALT and fasting insulin in patients who maintained weight loss was accompanied by a sustained reduction in hepatic steatosis and necroinflammatory activity. With long term weight maintenance there is likely to be an even greater resolution of hepatic fibrosis.
Overall, in our patient cohort, the decrease in ALT and insulin levels was associated with the amount of weight loss. However, a sustained improvement in ALT and insulin levels was seen with a weight loss of as little as 4–5% body weight without necessarily normalising BMI. These findings are in accordance with results of recent type 2 diabetes intervention studies where the average amount of weight loss was not large yet resulted in a substantial reduction in the incidence of diabetes.25–27
Without intervention, an average population weight gain of >1.5 kg/year could be expected.28
Completion of this intervention prevented expected annual weight gain for 84% of patients and maintained a significant weight reduction in 68% of patients. Waist circumference remained significantly below enrolment measurements in all but one patient, regardless of weight change during follow up. Six of 10 patients who regained weight reported continuing low levels of physical activity which may have contributed to a change in body fat distribution despite weight regain.
Our study was not designed to test the relative contribution of dietary changes, weight loss, or increased physical activity to the improvement in liver enzymes and insulin levels, and the individual effects of these components warrant further study.
One of the most important factors associated with successful weight maintenance was the continuation of appropriate levels of physical activity in the long term. Patients who regained weight had significantly higher than recommended exercise levels during the initial three months, suggesting that patients attempting unrealistic short term changes do not sustain these changes and may be more likely to relapse long term. Patients who maintained weight sustained recommended levels of activity during follow up. It is widely accepted that exercise has an important role in the treatment of visceral adiposity and insulin resistance. Our data further support the important role of exercise in the successful maintenance of weight loss in patients with chronic liver disease.
The other factor significantly associated with maintenance of weight loss was insulin resistance. Weight regain was inversely associated with insulin resistance—that is, less regain was observed in patients with higher HOMA and fasting insulin levels. Although controversial, a number of studies in different population groups have shown that hyperinsulinaemia predicts a reduced weight gain over time and may be an adaptation for weight maintenance.29,30
The mechanisms linking the association between insulin resistance and weight gain remain to be determined but this factor may be useful for predicting those patients at higher risk of weight regain after lifestyle interventions.
The success of weight maintenance in our study was probably due to the initial intensive programme combined with long term follow up. Increasing, the length and frequency of standard dietetic intervention improves long term success.31
In addition to the substantial cost of chronic liver disease to the health care system, the reduced HRQL in our patients illustrates the significant personal and social burden on those afflicted. Comorbid conditions such as obesity significantly contribute to the reduced feeling of well being in these patients, irrespective of disease severity. This study demonstrates that investment in weight reduction has the ability to reduce risk factors associated with progression of liver disease, decrease abnormal liver enzymes, improve quality of life, and in a proportion of patients improve histological features of liver injury. Importantly, these changes were achievable and sustainable with relatively small but persistent changes in lifestyle. These results suggest that treatment of overweight patients should form an important component of management of those with chronic liver disease.