Management of nonalcoholic fatty liver disease: An evidence-based clinical practice review

Table 1 Levels of evidence according to the study design

Level of evidence	Description
Type I	Evidence obtained from at least one well-designed, randomized, controlled1 trial or from a systematic review of randomized clinical studies
Type II	II-1 Evidence obtained from nonrandomized, prospective, controlled1 studies
	II-2 Evidence obtained from cohort observational studies2 or case-control studies, preferably multicenter
	II-3 Evidence obtained from case series
Type III	Opinions of authorities on the subject matter based on expertise, expert committees, case reports, pathophysiological studies or basic science studies

¹A controlled study is a study in which the intervention is managed by the researcher;

²An observational study is a study in which the intervention is not controlled by the researcher.

Table 2 Levels of recommendation according to the available evidence

Recommendation	Available evidence
A	The Consensus strongly recommends the mentioned intervention or service. This recommendation is based on high-quality evidence, with benefits that significantly exceed the risks
B	The Consensus recommends the regular clinical use of the mentioned intervention or service. This recommendation is based on moderate-quality evidence of benefits that exceed the risks
C	The Consensus does not make any positive or negative recommendations regarding the mentioned intervention or service. A categorical recommendation is not provided because the evidence (of at least moderate quality) does not show a satisfactory risk/benefit relationship. Decisions must be made on a case-by-case basis
D	The Consensus makes a negative recommendation against the mentioned intervention or service. The recommendation is based on at least moderate-quality evidence that does not show any benefit or where the risk or damage exceeds the benefits of the intervention
I	The Consensus concludes that the evidence is insufficient due to low-quality studies or heterogeneous results or because the risk/benefit balance cannot be determined

Table 3 Studies published on the effects of lifestyle changes in non-alcoholic fatty liver disease/nonalcoholic steatohepatitis patients

Ref.	Year	Study design1	Intervention1	Comparison	Duration (mo)	Histology	ALT
Scaglioni et al[218]	2012	OP-CS	D + E (n = 12)		3	N/A	+
Thoma et al[67]	2012	SR	D + E2 (n = 338)	Control (n = 98)	3-12	N/A	+
Keating et al[79]	2012	SR	Exercise (n = 439)	Non-exercise control	2-6	+	-
Peng et al[66]	2011	SR	D + E (n = 78)	Control (n = 67)	1-12	N/A	N/A
Browning et al[55]	2011	OP-CS	Low-carbohydrate diet (n = 18)	Hypocaloric diet (n = 18)	0.5	N/A	+
Moscatiello et al[41]	2011	OP-CS	Cognitive behavioral therapy (n = 68)	D + E (n = 82)	24	N/A	+
Kistler et al[73]	2011	OR-CS	Intense exercise (n = 213)	Moderate exercise (n = 162) and inactive (n = 438)		+	-
Elias et al[64]	2010	OP-CS	Diet 55% carbohydrates, 15% proteins and 30% fat (n = 17)	Control (n = 14)	6	N/A	+
Hayward et al[72]	2010	RCT	D + E (n = 28)	Control	6	+	+
2Promrat et al[45]	2010	RCT	LSC (n = 21)	Control (n = 10)	12	+	+
3Kantartzis et al[32]	2009	OP-CS	D + E (n = 50)	Control (n = 120)	9	N/A	+
St George et al[76]	2009	OP-CS	Exercise (n = 141)	Control (n = 34)	3	+	+
Chen et al[33]	2008	OP-CS	D + E (n = 16)	Exercise (n = 23) or control (n = 15)	2.5	N/A	+
Wang et al[34]	2008	OP-CS	LSC (n = 19)	Control (n = 38)	1	N/A	+
Krasnoff et al[69]	2008	OT-S	Exercise (n = 37)			+	N/A
Ryan et al[54]	2007	OP-CS	Diet 60% Carbohydrates/25% fat (n = 26)	Diet 40% Carbohydrates/45% fat (n = 26)	4	N/A	+
Tendler et al[219]	2007	OP-CS	Diet (n = 5)		6	+	-
Zelber-Sagi et al[80]	2006	RCT	D + E (n = 44)		6	+	+
Thomas et al[220]	2006	OP-CS	D + E (n = 10)		6	N/A	+
Sreenivasa Baba et al[35]	2006	OP-CS	D + E (n = 65)		6	N/A	+
4Huang et al[49]	2005	OP-CS	D + E (n = 23)		12	-	+
Suzuki et al[59]	2005	OP-CS	D + E (n = 348)		12	N/A	+
Hickman et al[50]	2004	OP-CS	D + E (n = 31)		15	+	+
Okita et al[221]	2001	OP-CS	Diet (n = 14)		6	N/A	+
Knobler et al[222]	1999	OP-CS	Diet (n = 48)		24	N/A	+
5Ueno et al[36]	1997	OP-CS	D + E (n = 15)	Control (n = 10)	3	-	+
Park et al[46]	1995	OP-CS	D + E (n = 13)	Control (n = 12)	12	N/A	+
Palmer et al[47]	1990	OR-CS	D + E (n = 39)		16	N/A	+
Eriksson et al[223]	1986	OT-S	Diet (n = 3)		12	N/A	+

Adapted from Satapathy et al[37].

¹For systematic review (SR), show data from articles based on randomized controlled trials; observational retrospective cohort studies (OR-CS), data show a comparison between groups with and without the studied variable; for randomized controlled trials, data show a comparison between groups at the end of the study period; for observational prospective cohort studies (OP-CS, includes studies with a prospective comparison of cohorts, and sole cohort with before/after comparison), data show a comparison within the same group considering the start and the end of the intervention period; in cases of transversal studies (OS-T), data show a comparison between groups (according to the variable) in the study period; for SR, data show a comparison of randomized controlled trials;

²Histologic improvement was observed in subjects who achieved a weight loss of ≥ 7%;

³Subjects with a reduction in hepatic steatosis according to magnetic resonance spectroscopy showed a significant reduction in alanine aminotransferase;

⁴Histologic improvement was observed in 9 of 15 subjects, which was not statistically significant regarding the comparison;

⁵Significant reduction in steatosis only in the D + E group, compared with baseline data, without differences in any histological parameters compared with the control. D + E: Diet and exercise; N/A: Not available; +: Significant reduction; -: No significant difference; LSC: Lifestyle changes; ALT: alanine aminotransferase.