Risk Prevention and Health Promotion for Non-Alcoholic Fatty Liver Diseases (NAFLD)

Round 1

Reviewer 1 Report

Khan Adnan and coll. in the article entitled "Risk Prevention and Health Promotion for Non-Alcoholic Fatty Liver Diseases (NAFLD)" give a complete and updated view of the main clinical and experimental knowledge on NAFLD.

Despite the completeness of the Authors' work, no mention is made of a possible new name for Fatty Liver Disease (FLD). In recent years it has been proposed to overcome the nomenclature “Non-Alcoholic Fatty Liver Disease” (NAFLD) and adopt the acronym MAFLD, or “Metabolic dysfunction-Associated Fatty Liver Disease”, giving relevance to the underlying condition of systemic metabolic dysfunction [Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-209]. MAFLD diagnosis would be based on the detection of hepatic steatosis (diagnosed by imaging, biomarkers, or histology) and at least one feature among overweight/obesity, type 2 diabetes, and metabolic dysregulation. The last criterium is met when at least two features are present among: increased waist circumference, arterial hypertension, hypertriglyceridemia, low HDL-C, prediabetes, insulin resistance, and subclinical inflammation. Interestingly, some observational studies have recently reported that the definition of MAFLD, compared with NAFLD, improves the identification of patients at higher risk of developing hepatic and extra-hepatic complications [Ayada, I.; van Kleef, L.A.; Alferink, L.J.M.; Li, P.; de Knegt, R.J.; Pan, Q. Systematically comparing epidemiological and clinical features of MAFLD and NAFLD by meta-analysis: Focusing on the non-overlap groups. Liver Int. 2022, 42, 277–287].
Moreover, the list of NAFLD COMPLICATIONS should include chronic kidney disease (CKD). I remember that NAFLD and CKD share some common pathophysiological mechanisms as well as some metabolic risk factors for cardiovascular disease. Some studies have confirmed that the presence of NAFLD increases the risk of CKD and that the degree of liver fibrosis is related to CKD stage. I quote two papers:

1. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: A Review of Links and Risks. Cheung A, Ahmed A. Clin Exp Gastroenterol. 2021 Nov 17;14:457-465. doi: 10.2147/CEG.S226130.
2. Influence of Nonalcoholic Fatty Liver Disease on the Occurrence and Severity of Chronic Kidney Disease. Tao Z, Li Y, Cheng B, Zhou T, Gao Y.J Clin Transl Hepatol. 2022 Feb 28;10(1):164-173. doi: 10.14218/JCTH.2021.00171.

Concluding remarks: on the first page line 34 I believe there is a small error - “over 800,000 people”; for glycated hemoglobin the usual abbreviation is HbA1c.

Author Response

We have included MAFLD and CKD onto our paper

-Thank you for your review

Reviewer 2 Report

This article provides a comprehensive review of NAFLD and is particularly helpful to the reader with a discussion and summary of the pharmacological aspects. However, there are some minor issues that need to be corrected.

Line 133. This sentence is weird

Line 568. SGLT2 is expressed in some hepatocyte cell lines. Please double-check if there is more direct evidence showing the liver has SGLT2 expression.

Thanks.

Author Response

line 133 and 568 were edited and revised. 

Thank you

Reviewer 3 Report

This is an review rather than an article. 

This paper systematically introduces NAFLD, including epidemiology, etiology, pathophysiology, screening, complications, and pharmacological therapies, especially the last one. However, nowadays some researchers have proposed MAFLD (metabolic associated fatty liver disease) to replace NAFLD. I think as an review summarizing the update of NAFLD, it should involve the content of MAFLD. Besides, liver biopsy is the gold standard for the diagnosis of NAFLD. Maybe I think there ought to add the content and pictures of NAFLD pathology. Third, the pathogenesis of NAFLD is very complex, which is hardly involved in this paper. This article summarizes the drug treatment of NAFLD very well, which is the biggest highlight of this article.

Author Response

MAFLD was included in our revisions. 

Round 2

Reviewer 3 Report

This paper  introduces NAFLD, including epidemiology, etiology, pathophysiology, screening, complications, and pharmacological therapies. The last one is the biggest highlight of this article. I think it is better to add liver pathology in the paper.