*Effectiveness of Lifestyle Interventions for Nonalcoholic Fatty Liver Disease Treatment DOI: http://dx.doi.org/10.5772/intechopen.106445*


**Table 1.** *A non-exhaustive table of studies that tried different potential pharmaceuticals for the treatment of NAFLD/NASH.*

#### *Effectiveness of Lifestyle Interventions for Nonalcoholic Fatty Liver Disease Treatment DOI: http://dx.doi.org/10.5772/intechopen.106445*

weight loss are challenging to achieve [104] and unfortunately, altering one's lifestyle alone does not always succeed, the different hurdles to adopting these changes are highlighted, along with strategies to overcome them.

A number of RCTs have demonstrated that altering one's lifestyle aids individuals with NAFLD in shedding pounds, lowering liver fat content, and raising their NAFLD activity score, which is a combination of steatosis, inflammation, and hepatic ballooning and is determined by liver biopsy. In a very recent meta-analysis of 30 RTCs involving 3280 participants with proven NAFLD, Fernandez et al., [104] found that combined exercise and diet intervention leads to significant reductions in ALT, AST, and HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) than diet or exercise alone. Also, Peterson and coworkers [105] reported a reversal of intrahepatic lipid in eight obese subjects following a 12-week moderately hypocaloric, very-low-fat (3%) diet (~1200 kcal/day) that led to a weight loss of only ~8 kg. Furthermore, in an RCT examining the effects of weight loss on clinical parameters of NASH, Promrat et al., [106] employed a 48-week ILI that combined diet, exercise, and behavior change, and targeting 7 to 10% weight loss, on 31 overweight/obese adults with biopsy-proven NASH. The patients were randomized in a 2:1 ratio to receive ILI or structured education (control). The change in NASH histological activity score (NAS) was the primary outcome (NAS ranges between 0 and 8) and is used to grade NAFLD: NAS ≥ 5 indicates NASH, and NAS ≤ 3 indicates no NASH [106]. In contrast to the control group, which lost 0.2% of weight after 48 weeks, patients allocated to ILI lost an average of 9.3% of their body weight. A significant correlation was observed between percent weight reduction and improvement in NAS (r = 0.497, P = 0.007). When compared to the control group (4.9 to 3.9), NAS dramatically improved in the ILI (from 4.4 to 2.0;P = 0.05). Compared to those who lost less than 7%, the patients who achieved the study weight loss goal significantly improved steatosis, lobular inflammation, ballooning injury, and NAS.

In an RCT undertaken by Katsagoni and coworkers in Greece [107], 63 ultrasonography-proven obese NAFLD patients with high ALT and/or GGT levels received 6 months of Mediterranean lifestyle intervention consisting of a Mediterranean diet (MD) along with guidance to increase physical activity and improve sleep habits. Compared to control patients, who received only written information for a healthy lifestyle, the Mediterranean lifestyle intervention patients showed a significant 50% reduction of ALT levels and liver stiffness after adjusting for % weight loss and baseline values. An RCT has looked at the impact of the green Mediterranean diet (GMD), which further restricts red and processed meat while enhancing green vegetables and polyphenols, on NAFLD as measured by intrahepatic fat (IHF) reduction [108]. In this 18-month study, 294 participants with abdominal obesity/dyslipidemia were divided into three weight-loss groups: healthy dietary guidelines (HDGs), MD, and green-MD, all of which included physical activity. NAFLD prevalence declined significantly to 54.8%, 47.9%, and 31.5% in HDG, MD, and GMD groups, respectively (p = 0.012 between groups). Even while the two MD groups experienced similar modest weight reduction, it is interesting to note that the GMD group experienced over twice as much intrahepatic fat (IHF) % loss (−38.9% proportionately) as compared to the MD and HDG groups.

In a very recent parallel, multicenter RCT, George and coworkers [109] looked at the impact of a Mediterranean diet (MD) on hepatic and metabolic outcomes in NAFLD. The 42 participants were randomized (1:1 ratio) to MD or low-fat diet (LFD) for 12 weeks. The results revealed that intrahepatic lipids and insulin resistance (measured by HOMA-IR) improved significantly within the LFD group but not within

the MD group. The visceral fat was reduced significantly in both groups. It is worth noting that this RCT did not involve any physical activity, which could have improved the results. Results from a recent [110] 52-week phase IV double-blind parallel RCT comparing the effects of lifestyle and dietary intervention plus Ezetimibe to lifestyle versus dietary intervention alone (placebo) on the progression and complications of NASH revealed that Ezetimibe administered in addition to lifestyle and dietary modification failed to significantly improve the histology of NASH beyond what is achieved with lifestyle and dietary modification alone.

In a 2-year RCT, Marin-Alejandro and colleagues examined the results of two customized dietary approaches in NAFLD patients [111]. The 98 participants were divided into two groups at random: the test group received the Fatty Liver in Obesity (FLiO) diet and the control group received the American Heart Association (AHA) diet. The AHA diet is based on AHA recommendations for eating habits and lifestyle changes, and it aims to reduce body weight by at least 3–5% and as much as 10% to reduce liver disease-related necrotizing inflammation. The FLiO diet is a Mediterranean diet that has the same targets as the AHA diet and is based on a quantitively and qualitatively good distribution of macronutrients, meal frequency, dietary behavior, antioxidant capacity, and lifestyle advice. The FLiO group outperformed the AHA group at the end of the study in terms of ALT, liver stiffness, and Fatty Liver Index, among other outcomes. However, weight loss percentage attenuates these differences when the analyses were adjusted. These results demonstrate that both approaches are viable substitutes for managing NAFLD. The FLiO method, however, might offer more long-lasting advantages in terms of metabolic and hepatic characteristics. Because of the limited space, only a few RTCs that reported the positive effect of lifestyle adjustments on NAFLD are reported above. **Table 2** shows some more similar RTCs conducted in the last 2 years.

#### **4. Barriers and facilitators to implementing a lifestyle change for NAFLD**

According to the evidence outlined in the previous section, NAFLD therapy based on intensive lifestyle intervention that combines diet and exercise can be successful. However, there are numerous obstacles to the clinical implementation of lifestyle intervention. For instance, the majority, if not all, intensive lifestyle therapies designed to improve NAFLD/NASH necessitate a weight loss of at least 5% of body weight. However, weight loss is notoriously difficult to achieve and even more challenging to maintain [119]. Without weight loss maintenance, the effect of ILI will, at best, be temporary. In a prospective observational cohort study, Jimenez and coworkers [110] evaluated the influence of weight regain on the NAFLD, assessed utilizing a fibrosis score 3 years post Roux-en-Y-gastric bypass surgery. They observed that of the 90 patients examined, 35.6% had obesity recurrence and that the fibrosis score in this group was significantly higher than in the group that had no weight regain. Similar to this, Nakanishi et al., [120] recently showed that among male participants who had been diagnosed with NAFLD and had entered remission, weight gain of 1.5 kg or more and a lack of exercise were related with NAFLD recurrence. The findings of these two studies strongly indicate that maintaining a weight loss is necessary to maintain NAFLD remission.

Additionally, the success of implementing ILI for NAFLD management requires the care to be best provided by multidisciplinary teams incorporating physicians who are experts in the management of NAFLD and its comorbidities, nutritionists,


*Effectiveness of Lifestyle Interventions for Nonalcoholic Fatty Liver Disease Treatment DOI: http://dx.doi.org/10.5772/intechopen.106445*


#### **Table 2.**

*Some of the RTCs undertaken between 2020 and the present to assess the lifestyle modifications on NAFLD. LFD: Low-fat diet; MD: Mediterranean diet; IHL: Intrahepatic lipids; ow/Ob: Overweight/obese; CD: Conventional diet; AHA: American Heart Association; FLiO: Fatty liver in obesity; PA: Physical activity; LGIMD: Glycemic index Mediterranean diet.*

educators, physical exercise coaches, as well as the patients' families. It also requires discipline, monitoring for complications, and regular laboratory assessments. The goal should be to foster an environment that promotes maintaining healthy body weight and body composition as a way of life. Another barrier to implementing ILI for NAFLD management is the lack of training necessary to deliver it among the health providers. In fact, a study by Avery et al., [121] has found a significant gap between recommendations and how clinical treatment is provided in reality. Healthcare professionals acknowledged a lack of knowledge and tools on how to successfully target lifestyle behavior change to control NAFLD over the long term and the necessity for a collaborative approach across disciplines to avoid miscommunicating with patients. Patients also supported this conclusion by reporting a severe shortage of information and support at the time of diagnosis and moving forward.

Patients must comprehend their disease to be convinced to adopt successful, long-lasting lifestyle adjustments. Impactful changes in their lifestyle habits will be hindered by their lack of knowledge of their condition and their failure to recognize the relationship between their current lifestyle choices and their disease, NAFLD, in this case. Patients must comprehend that if they make and sustain effective lifestyle adjustment, NAFLD/NASH may be curable [121].

Finally, it is important to remember that a variety of factors, including gender and reproductive status, genetics, the richness of the gut microbiota, endocrine and metabolic condition, and physical activity, may contribute to the variability of

#### *Effectiveness of Lifestyle Interventions for Nonalcoholic Fatty Liver Disease Treatment DOI: http://dx.doi.org/10.5772/intechopen.106445*

NAFLD. Therefore, the individual patient should consider all these factors to implement an individualized lifestyle adjustment. A one-size-fits-all lifestyle adjustments plan may not be adequate for all NAFLD patients. The impact of considering NAFLD heterogeneity on the development of targeted therapies for NAFLD is crucial for the success of the intervention [120].

A variety of lifestyle adjustment strategies and behavior change counseling techniques are available for usage, some with a more robust evidence base than others for addressing each stage in the process. These methods are intended to aid healthcare professionals and doctors in guiding patients toward making informed decisions about their actions and inspiring them to take ownership of their health. For instance, using motivational interviewing techniques during consultations can help patients feel more empowered to make their own health-related decisions. Some of the practical tips to support patients to make lifestyle changes include but not limited to 1) dispelling any myths, such as the idea that alcohol is the cause of NAFLD, by describing what NAFLD is and how it may be reversed with lifestyle changes; 2) explain the link between the body weight changes and the energy balance concept; 3) set a weight loss target that is realistic, personalized, quantifiable, attainable, and relevant; 4) encourage the use of self-monitoring tools, such as routine weighing, tracking calorie consumption by keeping a daily log, wearing activity trackers, understanding nutritional labels and choosing healthier options, acquiring knowledge of how to buy for, prepare, and serve meals; 5) utilize the proper interventions, such as regular meal patterns, fewer snacking, and portion control; 6) motivate patients to join local gyms, weight management programs, and walking groups; there is evidence that diet and physical activity interventions delivered in groups are effective in promoting clinically meaningful weight loss [122].

#### **5. Conclusion**

In the absence of an approved pharmacotherapy for NAFLD, ILIs remain the cornerstone for treating the condition. Strong evidence indicates that a sustained weight loss of 5% or more of the body weight can lead to NAFLD remission in a sizable proportion of patients. From the several RTCs listed in this study, lifestyle changes based on Mediterranean diets and exercise appear to be the most successful for improving NAFLD in a significant number of patients. Additionally, considering patient heterogeneity with regard to their reaction to ILIs, i.e. creating individualized ILI, may enhance the success of the intervention in NAFLD patient subgroups. In certain resistive patients, subtle changes in the composition of the meals or in exercise intensity may be more beneficial. As the number of NAFLD patients keeps increasing, health providers must have the ability and capacity within healthcare settings to motivate and support patients to make long-lasting lifestyle behavior adjustments. More emphasis should be placed on engaging patients in a discussion about their choices concerning their care. To better tackle NAFLD, healthcare providers should set up multidisciplinary teams with different expertise, i.e. hepatology, diabetology, cardiology, obesity, nutrition, and physical education.

Implementing effective lifestyle interventions for NAFLD patients is crucial not only because of the significant disease prevalence worldwide but also because excess liver fat is a separate risk factor for the onset of cardiovascular disease and T2D [123].
