Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

Abstract

Precision medicine defines the attempt to identify the most effective approaches for specific subsets of patients based on their genetic background, clinical features, and environmental factors. Nonalcoholic fatty liver disease (NAFLD) encompasses the alcohol-like spectrum of liver disorders (steatosis, steatohepatitis with/without fibrosis, and cirrhosis and hepatocellular carcinoma) in the nonalcoholic patient. Recently, disease renaming to MAFLD [metabolic (dysfunction)-associated fatty liver disease] and positive criteria for diagnosis have been proposed. This review article is specifically devoted to envisaging some clues that may be useful to implementing a precision medicine-oriented approach in research and clinical practice. To this end, we focus on how sex and reproductive status, genetics, intestinal microbiota diversity, endocrine and metabolic status, as well as physical activity may interact in determining NAFLD/ MAFLD heterogeneity. All these factors should be considered in the individual patient with the aim of implementing an individualized therapeutic plan. The impact of considering NAFLD heterogeneity on the development of targeted therapies for NAFLD subgroups is also extensively discussed.

The Risk of Colorectal Adenoma in Nonalcoholic or Metabolic-Associated Fatty Liver Disease

“…Consistent with our results, diabetes was proven to be an independent risk factor for colorectal adenoma [40]. In this study, individuals with advanced fibrosis defined by the FIB-4 index were significantly associated with increased colorectal adenoma in both NAFLD and MAFLD patients, in agreement with previous studies [32,41], and this approach is in line with the implementation principles of precision medicine in NAFLD/MAFLD [42].…”

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“…This also would help to select the most appropriate treatment for a given patient following the precision medicine principles. 13,15 Thus, in the future, it can be envisaged that precise phenotyping of pathogenic pathways would lead to select a specific drug 10 or that a genetic treatment 27,186 could be chosen based on global ethnic-specific genetic information. Also, it is likely that principles of precision nutrition 187 and precision exercise 188 would apply to patient management to increase the therapeutic efficacy of lifestyles changes in NAFLD management.…”

“…12 Thus, more granular data on the effectiveness of new therapies in NAFLD subgroups is needed to create the proper grounds for personalized or precision medicine approaches in the near future. [13][14][15] As mentioned above, the NAFLD acronym groups a heterogeneous patient population. NAFLD clinical expression results from a complex and multilayered dynamic interaction of different factors including sex, 16 presence of several genetic variants, 17 coexistence of different comorbidities, 18 diverse microbiota composition, [19][20][21] and various degrees of alcohol consumption 22 among others.…”

Insights into Nonalcoholic Fatty-Liver Disease Heterogeneity

“… 12 Thus, more granular data on the effectiveness of new therapies in NAFLD subgroups is needed to create the proper grounds for personalized or precision medicine approaches in the near future. 13 14 15 …”

“…12 Thus, more granular data on the effectiveness of new therapies in NAFLD subgroups is needed to create the proper grounds for personalized or precision medicine approaches in the near future. [13][14][15] As mentioned above, the NAFLD acronym groups a heterogeneous patient population. NAFLD clinical expression results from a complex and multilayered dynamic interac-tion of different factors including sex, 16 presence of several genetic variants, 17 coexistence of different comorbidities, 18 diverse microbiota composition, [19][20][21] and various degrees of alcohol consumption 22 among others.…”