MAFLD, formerly known as non-alcoholic fatty liver disease (NAFLD), is distinguished by hepatic steatosis and the presence of one or more of the following factors: overweight/obesity, type 2 diabetes mellitus (T2DM), or indications of metabolic dysregulation (1). Strikingly, MAFLD affects approximately a quarter of the population worldwide with a rising trend (2) and involves a spectrum of liver diseases that range from simple steatosis to its progressive form, non-alcoholic steatohepatitis (NASH), characterized by inflammation and progressive tissue fibrosis, and may lead to the development of cirrhosis and even hepatocellular carcinoma (HCC) (2). Moreover, MAFLD aggravates the deteriorative progression of T2DM and its complications (3), and significantly increases the risk of chronic kidney disease (CKD) (4) along with cardiovascular disease (5). Nevertheless, the clinical management of MAFLD is currently restricted to lifestyle interventions with no approved drug therapy for the disease.

It has been widely accepted that chronic inflammation and fibrosis formation play pivotal roles in the pathogenesis of MAFLD (6). In a physiological state, the hepatic inflammatory response is a response to various stress conditions, which is beneficial to repairing tissue damage and promoting hepatic homeostasis (7). However, prolonged or intense inflammatory reactions may result in irreversible liver damage, such as liver fibrosis, which is triggered by the activation of hepatic stellate cells (HSCs) and their transdifferentiation into myofibroblasts (8). According to the “multiple hit” hypothesis, a comprehensive and detailed theory focusing on the pathomechanism of MAFLD, inflammation may precede steatosis in NASH, and inflammatory mechanisms are involved in the entire process of MAFLD (9). Moreover, synergistic effects of pathological events, such as endoplasmic reticulum (ER) stress (10), insulin resistance (11), aberrant lipid metabolism (12), oxidative stress (13), and mitochondrial dysfunction (14), make great contributions to the exacerbation of inflammation and the deterioration of fibrogenesis via various pathways, and have all been implicated in the progression of MAFLD. Therefore, it is meaningful to illustrate and summarize the research trend on inflammation and fibrogenesis in MAFLD with the hope of discovering drug targets and developing effective therapies.

Comparatively to literature reviews, bibliometrics conducts quantitative research on the field’s literature by analyzing its characteristics with the help of visualizing processing tools, like CiteSpace or VOSviewer, to identify the predominant institutions/countries, leading authors and journals, top-cited references, research trend, or hotspots (15). Considering that hepatic inflammation and fibrogenesis are of great importance in the progress of MAFLD, no bibliometric study has been reported on this topic. Therefore, our study aims to identify the publication trends and potentially significant hotspots on inflammation and fibrogenesis in MAFLD by analyzing the records published from 2000 to 2022.

In this bibliometric analysis study, we found 2,348 articles regarding inflammation and fibrogenesis in MAFLD from 2000 to 2022 in the WoSCC-SCIE. With the help of VOSviewer and CiteSpace software, our study analyzed publication trends about inflammation and fibrogenesis in MAFLD from all aspects to shed light on researchers interested in this field.

Between 2000 and 2013, less than 100 articles concerning inflammation and fibrogenesis in MAFLD were published per year globally. However, the number of papers has increased rapidly since 2018, which was associated with the renaming of NAFLD and its high morbidity, indicating that the research on inflammation and fibrogenesis in MAFLD has caught the attention of researchers worldwide. Table 1 shows that the USA played a vital role in the research on inflammation and fibrogenesis in MAFLD. Notably, with the development of China’s medical and scientific research capability, the number of articles published in China has rapidly increased and firstly surpassed the USA in 2021. Moreover, with the development of globalization, international cooperation has become a new trend that benefits the output of high-quality research. The collaborations between countries/regions are shown in Figure 3 , most (n = 6) of the top 10 productive countries/regions cooperated closely with other countries, but China greatly needs to strengthen its cooperation with other countries.

Remarkably, 7 of the top 10 productive institutions and 7 of the top 10 most cited journals are from the USA, reasonably explaining that the USA occupies the main contribution on total numbers of published papers. Therefore, these results demonstrated that the USA played a dominant role in the world’s academic activities. However, China may be a rising star in the next few years, considering the number of papers published in this field and its rising trends.

The timeline view in Figure 7 indicates the evolution of the research trend. We found that early research concentrated on adiponectin and morbid obesity. Adiponectin is an adipocyte-specific secretory protein that plays a pivotal role in glycolipid metabolism (34) and extracellular matrix (ECM) metabolism (35) and has made a great contribution to preventing the liver from steatosis, inflammation, and fibrosis (36, 37). It has been reported that MAFLD patients have significantly lower plasma adiponectin levels (38). Multivariate regression analysis identifies decreased adiponectin as an independent risk factor of hepatic steatosis (37). Furthermore, abundant clinical and basic studies have illustrated that adiponectin agonists are therapeutic targets for NAFLD therapy (39, 40). Morbid obesity was defined as a body mass index (BMI) of at least 40 kg/m². Many researchers suggest that Roux-en-Y gastric bypass (RYGB) surgery is a decent curative method in morbid obesity patients with MAFLD to improve inflammation and fibrosis and then inhibit malignant progression to NASH (41–43). Subsequently, interim research mainly focused on identifying novel markers and cellular and molecular mechanisms in MAFLD (44, 45).

With the deepening study in this field, there is increasing evidence to show that MS is an important risk factor in MAFLD, vividly illustrated by the renaming of NAFLD to MAFLD. MS mainly refers to hyperglycemia, abdominal obesity, and dyslipidemia. A systematic review attempted to estimate the prevalence of MAFLD among patients with T2DM and found that the prevalence of MAFLD was 55.5% among 49,419 T2DM patients (46). Another research suggested that more than 90% of obese patients with T2DM also have MAFLD (47), indicating that MAFLD is strongly associated with hyperglycemia. Moreover, studies among T2DM participants have demonstrated that plasma glucose level is positively correlated with the risk of developing advanced liver disease (HCC) (48). Furthermore, glycemic variability, except for hyperinsulinemia and hyperglycemia, is an independent predictive factor for the progression of hepatic fibrosis in MAFLD (49). Considering that there is no approved drug for NASH to date, lifestyle interventions and combinations of drugs, which can effectively regulate glucose and lipid metabolism and reduce liver inflammation and fibrosis, might be a beneficial option to curb the deteriorated progression of MAFLD. Even new drug development focuses on the restitution of metabolic derangements and halting inflammatory and fibrogenic pathways, showing that MS plays an important role in the development of MAFLD (50).

Furthermore, it has been reported that genetic factors took part in the progression of MAFLD due to the upgrading and improvement of new genomic and proteomic technologies (51), and many risk variants of the NAFLD population were identified by a genome-wide association study (GWAS) (52). Currently, at least five variants in different genes are associated with the development and progression of MAFLD, namely, PNPLA3, TM6SF2, GCKR, MBOAT7, and HSD17B13 (53–55). Some of them are associated with an increased risk of T2DM. Others are associated with the risk of developing obesity (56, 57), indicating that MAFLD might have shared mechanisms that are involved in the pathogenesis of T2DM and obesity, emphasizing the importance of MS in MAFLD, and supporting the renaming of NAFLD to MAFLD (55).

Gut microbiota is another research hotspot now. Many studies showed that microbiota might improve or aggravate MAFLD through multiple mechanisms (58–60), including changing the permeability of the intestine (61), altering the expression of genes involved in the de novo lipogenesis (62), and regulating choline (63) and bile acid metabolism (64). The most extensively studied microbial molecule is lipopolysaccharide (LPS), which is produced by Gram-negative bacteria. It has been reported that systemic LPS concentration was significantly elevated in rats treated with HFD and high-sucrose diet (65) and in MAFLD patients (66). In related animal studies, the effect of LPS on the development of MAFLD has also been shown in mice injected with LPS and mice lacking toll-like receptor 4 (TLR4) (67, 68). A number of studies investigated that modulation of the gut microbiota may be a potential therapeutic target for MAFLD, including using antibiotics, prebiotics, and probiotics (69).

Generally speaking, Figure 7 demonstrates that the research hotspots have shifted their direction to MS, genetics, and the microbiome in the study of inflammation and fibrosis in MAFLD.

Another effective method of reflecting the transition of hotspots in an academic area is to use keyword bursts. The top 25 keywords with the strongest citation bursts are shown in Figure 8 . Among them, three keywords continue to last by the end of 2022. The first one is management. The related research with the highest citation was published in Hepatology in 2019, elucidating that gut microbiota profile and systemic inflammatory response in NAFLD were closely related, further promoting the process of HCC (70). Some of the works concerned the relationship between MAFLD and common chronic diseases (71, 72), and most publications explored effective methods to curb the development of MAFLD and its complications (73–76). The second one was fibrosis stage, a valuable parameter to predict all-cause and liver disease-related mortality in MAFLD (77). The related articles mainly focused on seeking potential ways to restrain the adverse progression of fibrosis stage and thus improve the prognosis (78–80). For example, Khurana and Wang attempted to find an invasive method that is helpful for early diagnosis, distinguishing disease staging, and giving personalized treatments (81, 82). The third keyword burst, which started in 2019, was stress. Articles related to this keyword refer to a metabolic stress state relevant to the dysfunction of mitochondria and ER and describe its potential mechanisms that have a significant impact on the progress of MAFLD. Zhang et al. suggested that impaired mitophagy, which may lead to the accumulation of excessive ROS production and oxidative stress, triggered hepatic NLRP3 inflammasome activation during the progress of MAFLD (83). In addition, another research noted that down-regulating the NLRP3/NF-κB signaling pathway can attenuate inflammation in mouse liver (84). Meanwhile, the authors identified apoptosis signal-regulating kinase 1 (ASK1) as a suppressor of NASH and fibrosis formation via ASK1 knockout experiments. All of them reminded us that inflammation and fibrosis are key factors in the development of MAFLD and drugs that act on them may have potential as a clinical treatment to prevent MAFLD in humans.

Of note, magnetic resonance elastography (MRE), a keyword that lasted from 2017 to 2019, is a non-invasive evaluation to distinguish healthy people from those with NAFLD and assess the degree of fibrosis to discriminate simple steatosis from NASH (85), showing that colleagues are actively looking for non-invasive methods to determine the severity of NAFLD, and thus ensure timely and optimal treatment.

Notably, the number of publications focusing on inflammation and fibrosis in MAFLD increased rapidly. However, previous studies on inflammation and fibrogenesis in MAFLD still have certain limitations, and there is much to be improved in the future.

Our study has some limitations. First, we only analyzed data exported from WoSCC-SCIE to undertake relevant analysis, which may result in selection bias. Second, this study excluded non-English literature, and some high-quality non-English literature was excluded. Third, VOSviewer and CiteSpace have certain defects that may output discredited results. Nevertheless, our study still provides significant information and insights for researchers interested in this field.

From 2000 to 2022, the number of articles focusing on inflammation and fibrosis in MAFLD increased rapidly, especially in the last 5 years. The USA played a vital role in the development of this topic regarding the number of publications, international cooperation with other countries, and achievements of authors. However, China may be a rising star in this research field with its increasing trend in the number of publications and its huge population. Current research mainly focuses on MS, genetics, and microbiome. Considering the urgent and emergent situation of inflammation and fibrosis in MAFLD, more studies are needed to focus on developing novel drugs and identifying non-invasive biomarkers. In short, our study provides a comprehensive overview of this discipline, which could more precisely direct scholars in future research and provide valuable guidance for clinical diagnosis, appropriate treatment, and individualized prevention.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

All the authors have contributed significantly. HL designed the study. KL and YC wrote the manuscript. KL, YC, SF, SW, and ZW collected and analyzed the data, participated in discussion. SF and HL supervised the study and corrected the manuscript. All authors contributed to the article and approved the submitted version.