Table 3.

Recommendations about the management of confounders in NAFLD clinical trials.

Metabolic and lifestyle confounders on NAFLD clinical trials	Recommendations
Current or recent history (<5 years) of significant alcohol consumption before the screening.	-Consumption <30 g per day for men and <20 g per day for women. -Assess the pattern of alcohol intake (e.g., binge drinking). -Perform questionnaires routinely (e.g., AUDIT).
Engagement in an active weight loss program or taking weight loss medication.	-Weight loss of less than 5% within 6 months prior to randomisation. -Lack of history or planned efficient bariatric surgery prior to screening.
Changes in the lifestyle due to the enrolment (Hawthorne effect).	-Provide practical but uniform diet and physical activity recommendations: a) avoidance of sugar-sweetened beverages; b) consumption of a healthy and well-balanced diet; c) moderate-to-high intensity exercise daily; d) less than 2 hours/day of screen time.
Patients with decompensated diabetes (HbA1c >9.0%).	-Controlled diabetes, defined as HbA1c <9.0% within 60 days prior to enrolment.
Taking drugs known to have potential therapeutic activity on NASH prior to entry into the study (e.g., vitamin E, GLP-1 agonists).	-Change the prescription, if possible. -Maintain a stable dose 3 months before the enrolment and during the clinical trial. -Randomisation controlled by potential hidden combination therapy. -Not to prescribe these drugs during the follow-up.
Taking drugs that can induce steatosis/steatohepatitis (e.g., steroids).	-Try to substitute the steatogenic drugs before the enrolment or, at least, maintain a stable dose.