Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis

Abstract

Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that is strongly associated with obesity. Currently, there is no approved therapy for NASH. Weight reduction is typically recommended, but efficacy data are lacking. We performed a randomized controlled trial to examine the effects of lifestyle intervention using a combination of diet, exercise, and behavior modification, with a goal of 7% to 10% weight reduction, on clinical parameters of NASH. The primary outcome measure was the change in NASH histological activity score (NAS) after 48 weeks of intervention. Thirty-one overweight or obese individuals (body mass index [BMI], 25-40 kg/m(2)) with biopsy-proven NASH were randomized in a 2:1 ratio to receive intensive lifestyle intervention (LS) or structured education (control). After 48 weeks of intervention, participants assigned to LS lost an average of 9.3% of their weight versus 0.2% in the control group (P = 0.003). A higher proportion of participants in the LS group had a reduction of NAS of at least 3 points or had posttreatment NAS of 2 or less as compared with the control group (72% versus 30%, P = 0.03). NAS improved significantly in the LS group (from 4.4 to 2.0) in comparison with the control group (from 4.9 to 3.5) (P = 0.05). Percent weight reduction correlated significantly with improvement in NAS (r = 0.497, P = 0.007). Participants who achieved the study weight loss goal (>or=7%), compared with those who lost less than 7%, had significant improvements in steatosis (-1.36 versus -0.41, P < 0.001), lobular inflammation (-0.82 versus -0.24, P = 0.03), ballooning injury (-1.27 versus -0.53, P = 0.03) and NAS (-3.45 versus -1.18, P < 0.001).

Conclusion: Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH.

Figure 1

Enrollment of study participants.

Figure 2a

Percent weight change (mean±SE) by group at 6 and 12 months. P<.001 for the comparison between lifestyle and control at month 6, and P = 0.003 for the comparison at month 12.

Figure 2b

Body Mass Index (BMI) change (mean±SE) by group at 6 and 12 months. P<.001 for the comparison between lifestyle and control at month 6, and P = 0.004 for the comparison at month 12.

Figure 3

Serial mean alanine aminotransferase (ALT) values (mean±SE) by group at 0, 6 and 12 months. P= <.001 for the comparison between lifestyle and control at month 6, and P = 0.01 for the comparison at month 12.

Figure 4

Scatterplot with slope line depicting change in participant NASH Activity Score (NAS) as a function of their percent weight change. The slope line shows the trend (r=−.497, p=0.007) for participants who lost more weight to change more NAS points. Each point on the graph represents one study participant. Solid circle indicates Lifestyle intervention group. Triangle with no fill indicates Control group. Points to the right of the dashed vertical line indicate those who achieved the study end point of a 3 point reduction in NAS (study end point)