Efficacy of acupoint catgut embedding therapy for phlegm-turbidity and blood-stasis metabolic dysfunction-associated fatty liver disease

Abstract

BACKGROUND

No optimal treatment has been established for metabolic dysfunction–associated fatty liver disease with phlegm-turbidity and blood-stasis syndrome (MAFLD-PTBS), highlighting the need for more effective therapeutic approaches.

AIM

To elucidate the clinical effectiveness of acupoint catgut embedding therapy (ACET) for MAFLD-PTBS and preliminarily examine its association with biomarkers, particularly platelet-derived growth factor (PDGF).

METHODS

We retrospectively enrolled 80 patients with MAFLD-PTBS, divided into an ACET group (n = 40) receiving ACET therapy and a control group (n = 40) treated with conventional hepatoprotective and enzyme-lowering oral medications. Therapeutic outcomes were compared between the groups. Changes in body mass index (BMI), abdominal circumference (AC), body weight (BW), total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver stiffness measurement (LSM), a four-item liver fibrosis panel, and serum concentration of PDGF, transforming growth factor-β1 (TGF-β1), and cytokeratin 18 (CK-18) were assessed before and after treatment.

RESULTS

Significant differences were observed both within group (pre- vs post-treatment) and between group post-intervention for all measured indicators, including BMI, AC, BW, TC, TG, ALT, AST, LSM, liver fibrosis indices, PDGF, TGF-β1, and CK-18 (all P < 0.05).

CONCLUSION

ACET exhibits promising clinical effectiveness for managing MAFLD-PTBS, with effects closely associated with serum concentrations of PDGF, TGF-β1, and CK-18.

Key Words: Acupoint catgut embedding; Phlegm-turbidity and blood-stasis syndrome; Metabolic dysfunction–associated fatty liver disease; Platelet-derived growth factor

Core Tip: This study included 80 patients with metabolic dysfunction–associated fatty liver disease with phlegm-turbidity and blood-stasis syndrome (MAFLD-PTBS). Multiple diagnostic indicators were evaluated, and the results revealed significant clinical efficacy of acupoint catgut embedding in this population. The therapeutic effects were closely associated with serum concentrations of platelet-derived growth factor, transforming growth factor-β1, and cytokeratin 18. These results suggest that acupoint catgut embedding may serve as a valuable therapeutic option and provide relevant guidance for managing MAFLD-PTBS.

INTRODUCTION

Metabolic dysfunction-associated fatty liver disease (MAFLD), a metabolic disorder-driven condition characterized by hepatic steatosis, is highly prevalent and associated with a considerable mortality rate[1]. Affecting approximately one-third of the global population, MAFLD carries profound clinical implications, with potential progression to advanced hepatic complications such as end-stage liver disease, hepatocellular carcinoma, and liver failure. Additionally, it is linked with increased risks of all-cause, cardiovascular, and cancer-related mortality[2,3]. Several factors contribute to MAFLD susceptibility. In addition to chronic exposure to air pollutants, established risk factors include male sex, tobacco use, alcohol consumption, abdominal obesity, and excessive dietary fat intake, all of which may exacerbate disease progression[4]. The pathogenesis of MAFLD is multifactorial and involves complex interactions among the gut microbiota, intestinal function, and hepatic metabolism, which are established as key mechanisms in disease development[5]. Current therapeutic strategies primarily focus on three pathological processes-reducing hepatic steatosis, alleviating chronic inflammation, and inhibiting fibrotic progression-while simultaneously addressing associated cardiometabolic risk factors. However, no universally accepted optimal treatment regimen has yet been established[6], highlighting the need for novel therapeutic interventions to improve clinical outcomes. Phlegm-turbidity and blood-stasis syndrome, characterized by obstruction of the meridians due to phlegm accumulation and blood stasis, is a pathological state associated with dysfunction of the zang-fu organs[7]. In metabolic dysfunction–associated fatty liver disease with phlegm-turbidity and blood-stasis syndrome (MAFLD-PTBS) presents primarily as liver–spleen disharmony, leading to the intermingling of phlegm and blood stasis, which in turn obstructs the liver collaterals. Clinically, this condition manifests as fatty liver deposits, inflammation, and fibrosis[8]. Acupoint catgut embedding therapy (ACET) involves the implantation of absorbable catgut into specific acupoints to prevent and treat diseases[9]. Reported as a safe and effective intervention for weight management, ACET has been shown to reduce body weight (BW) and waist circumference in perimenopausal women with central obesity, partly through the modulation of intestinal flora[10]. Additionally, ACET has been documented to contribute to sustained weight control, an effect associated with appetite modulation in overweight and obese populations[11]. Previous research has included a relatively small number of studies on the application of ACET for MAFLD-PTBS. Therefore, this study employed ACET in patients with MAFLD-PTBS to preliminarily examine its potential therapeutic mechanisms.

MATERIALS AND METHODS

Participant selection

This retrospective study included 80 outpatients and inpatients diagnosed with MAFLD-PTBS who were recruited from the Hepatology Department and the Acupuncture-Moxibustion Department of Taizhou Hospital of Traditional Chinese Medicine (TCM). The study protocol was approved by the Institutional Ethics Committee of Taizhou Hospital of TCM. Diagnosis based on Western medicine followed the Guidelines for Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease issued by the Fatty Liver and Alcoholic Liver Disease Study Group of the Chinese Medical Association Hepatology Branch[12]. TCM diagnosis was conducted in accordance with the standards established by the Digestive System Disease Committee of the Chinese Integrative Medicine Association and the Spleen-Stomach Disease Branch of the Chinese TCM Association[9,13]. Exclusion criteria included were as follows: (1) Individuals with uncontrolled dietary habits, particularly excessive fat intake or alcohol consumption; (2) Patients with hepatitis or cirrhosis resulting from viral infection, drug toxicity, autoimmune disorders, or other known etiologies; (3) Women who were pregnant, lactating, or planning pregnancy during the treatment period; (4) Individuals with alcohol dependence or other conditions unsuitable for pharmacological evaluation; (5) Insulin-dependent diabetes mellitus or non-insulin-dependent diabetes with severe complications; (6) Patients with significant comorbidities affecting the cardiovascular, hepatic, renal, or hematopoietic systems, or those with psychiatric disorders; and (7) Cases failing to meet inclusion criteria, exhibiting non-compliance with treatment protocols, or having insufficient data for assessment of efficacy or safety.

Group allocation and interventions

Participants were assigned to either the ACET group or a control group, with 40 individuals in each arm. Baseline comparability of the study groups was confirmed, as statistical analysis of demographic and clinical variables-including sex, age, disease duration, and fatty liver grading-revealed no significant differences between the groups (P > 0.05). ACET was performed as follows: The patient was positioned supine, and the treatment area was exposed, marked, and sterilized with an iodine solution. A 000-gauge absorbable collagen suture (Yangzhou Guoxiang Medical Instrument Factory) was loaded into the distal end of a disposable No. 7 embedding needle, which was then fitted with a stylet. The needle was inserted into the predetermined acupoint and required depth. Upon eliciting the characteristic needling sensation (Deqi), the needle core was advanced while the tube was withdrawn, embedding the suture into the subcutaneous tissue or muscle layer. The insertion site was subsequently compressed to prevent bleeding and ensure the suture was fully retained, and an adhesive bandage was applied to protect the puncture site. The procedure was repeated every 2 weeks, with therapeutic outcomes evaluated after six sessions (12 weeks). Participants in the control group received standard hepatoprotective and enzyme-lowering oral medications over the same 12-week period.

Baseline data collection

Participant information-including age, sex, disease duration, body mass index (BMI), and family history-was recorded to facilitate comprehensive comparative analyses.

Clinical outcome evaluation

Therapeutic effectiveness was categorized as cured, markedly effective, effective, or ineffective. Patients were considered cured if they exhibited complete resolution of clinical manifestations, normalization of hepatic ultrasonography findings, and ≥ 70% improvement in serological parameters. Markedly effective outcomes were defined by notable symptom alleviation, a two-grade reduction in liver ultrasound grading, and 30%-70% improvement in serological parameters. Effective responses were characterized by partial symptom relief, a one-grade improvement in ultrasonographic evaluation, and a ≤ 30% improvement in serological parameters, whereas ineffective responses indicated minimal or no symptom improvement, no change or deterioration in hepatic ultrasonography findings, or worsening of serological parameters. The total effective rate was calculated as follows: Total effective rate = Cured rate + Markedly effective rate + Effective rate.

Obesity assessment

The degree of obesity was evaluated by measuring pre- and post-treatment BMI, abdominal circumference (AC), and BW in both study groups. BMI was calculated from height and weight measurements obtained using a height-weight scale, with participants barefoot and without headwear. Overweight or obesity was defined as a BMI value of ≥ 23 kg/m²[14]. AC was measured with participants standing at the end of a normal expiration, using a flexible tape positioned horizontally at the midpoint between the iliac crest and the lowest rib; central obesity was defined according to Chinese guidelines as an AC ≥ 90 cm for men or ≥ 85 cm for women[15]. BW was recorded directly from the scale.

Total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase measurements

Blood samples were collected to measure these parameters using an automated biochemical analyzer. The optimal reference ranges were defined as < 5.2 mmol/L for total cholesterol (TC), < 1.7 mmol/L for triglycerides (TG), < 50 U/L for men or < 40 U/L for women for alanine aminotransferase (ALT), and < 40 U/L for aspartate aminotransferase (AST)[16].

Liver fibrosis severity evaluation

Liver stiffness measurement (LSM) was performed using FibroScan technology[4], with measurements obtained between the seventh and eighth or eighth and ninth intercostal spaces along the right mid-axillary to anterior axillary line. For each participant, 10 consecutive valid measurements were recorded, and the median value was used as the final result, expressed in kilopascals (kPa). Additionally, fasting blood samples were obtained after an overnight fast of more than 8 hours in the morning, both before and after treatment. Approximately 5 mL of whole blood was allowed to clot naturally and then centrifuged at 2500 rpm for 10 minutes to isolate serum. The resulting supernatant was aliquoted and stored at -80 °C for subsequent quantification of liver fibrosis markers, including hyaluronic acid, laminin, type III procollagen, and type IV collagen.

Platelet-derived growth factor (PDGF), transforming growth factor-β1 (TGF-β1), and cytokeratin 18 (CK-18) Determination: Serum concentrations of PDGF, TGF-β1, and CK-18 were quantitatively measured in pre- and post-treatment samples using ELISA, with all assays conducted in strict accordance with standardized experimental protocols.

Statistical analysis

All statistical analyses were conducted using SPSS version 19.0, with results presented as mean ± SD. For normally distributed data with homogeneity of variance, comparisons between groups were performed using the independent samples t-test. Relationships between variables were evaluated using Spearman’s rank correlation coefficient. Statistical significance was defined as P < 0.05.

RESULTS

Baseline characteristics

The baseline characteristics of the study participants are summarized in Table 1. Comparative analyses revealed no statistically significant differences between groups with respect to age, sex distribution, disease duration, BMI, or family history (P > 0.05).

Table 1 Participants’ baseline characteristics.

	Age (years)	Male	Illness duration (d)	BMI (kg/m2)	Family history
ACET group (n = 40)	34.23 ± 8.08	22 (55.00)	15.45 ± 8.71	31.00 ± 4.37	4 (10.00)
Control group (n = 40)	38.38 ± 12.15	25 (62.50)	14.15 ± 6.52	29.95 ± 3.75	3 (7.50)
t/χ2	1.799	0.464	0.756	1.153	0.157
P value	0.076	0.496	0.452	0.252	0.692

ACET: Acupoint catgut embedding therapy; BMI: Body mass index.

Treatment outcomes

As presented in Table 2, the overall therapeutic efficacy was significantly higher in the ACET group than the control group, with rates of 92.50% and 75.00%, respectively (P < 0.05).

Table 2 Clinical efficacy comparison, n (%).

	Cured	Markedly effective	Effective	Ineffective	Overall effectiveness
ACET group (n = 40)	12 (30.00)	18 (45.00)	7 (17.50)	3 (7.50)	37 (92.50)
Control group (n = 40)	8 (20.00)	11 (27.50)	11 (27.50)	10 (25.00)	30 (75.00)
χ2					4.501
P value					0.034

ACET: Acupoint catgut embedding therapy.

Changes in obesity-related parameters

Obesity-related parameters are summarized in Table 3. No significant differences were observed between the groups at baseline (P > 0.05). Post-treatment, both groups exhibited notable reductions in BMI, AC, and BW (P < 0.05). Post-treatment comparisons revealed that reductions in these parameters were significantly greater in the ACET group than in the control group (P < 0.05).

Table 3 Comparative analysis of body mass index, abdominal circumference, and body weight.

		BMI (kg/m2)	Abdominal circumference (cm)	Body weight (kg)
ACET group	Before treatment	28.01 ± 1.37	112.28 ± 18.16	81.25 ± 10.70
	After treatment	24.25 ± 1.26a	91.83 ± 15.84a	66.72 ± 12.40a
Control group	Before treatment	27.64 ± 1.42	110.22 ± 15.93	77.47 ± 10.74
	After treatment	24.28 ± 1.39b	107.60 ± 18.00b	72.00 ± 8.92b

^aP < 0.05, pre- vs post-treatment in the acupoint catgut embedding therapy (ACET) group.

^bP < 0.05, ACET vs control post-treatment.

ACET: Acupoint catgut embedding therapy; BMI: Body mass index.

TC, TG, ALT, and AST comparisons

Changes in TC, TG, ALT, and AST are summarized in Table 4. These indices showed comparable baseline levels between the groups (P > 0.05). Post-treatment, both groups exhibited significant reductions in all parameters (P < 0.05). Post-treatment comparisons indicated that reductions in TC, TG, ALT, and AST were significantly greater in the ACET group than in the control group (P < 0.05).

Table 4 Total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase comparisons.

		TC (mmol/L)	TG (mmol/L)	ALT (U/L)	AST (U/L)
ACET group	Before treatment	4.86 ± 0.99	3.41 ± 1.72	130.09 ± 54.31	44.28 ± 43.95
	After treatment	4.27 ± 0.76a	2.19 ± 0.73a	39.62 ± 17.58a	36.86 ± 47.30a
Control group	Before treatment	4.73 ± 0.47	3.30 ± 1.65	121.70 ± 60.3	51.26 ± 38.73
	After treatment	4.61 ± 0.52b	3.04 ± 1.12b	69.56 ± 33.83b	46.86 ± 49.69b

^aP < 0.05, pre- vs post-treatment in the acupoint catgut embedding therapy (ACET) group.

^bP < 0.05, ACET vs control post-treatment.

TC: Total cholesterol; TG: Triglyceride; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ACET: Acupoint catgut embedding therapy.

LSM and a four-item liver fibrosis panel

Measurements of liver stiffness and the four-item liver fibrosis panel obtained through FibroScan are presented in Table 5. Baseline comparisons revealed no significant differences between the groups (P > 0.05). Post-treatment, both cohorts exhibited substantial reductions in LSM and liver fibrosis panel parameters (P < 0.05). Post-treatment comparisons indicated that these reductions were significantly greater in the ACET group than in the control group (P < 0.05).

Table 5 Comparison of instantaneous liver stiffness measurement and liver fibrosis panel.

		Instantaneous LSM (KPa)	HA (μg/mL)	LN (μg/mL)	PCIII (μg/mL)	IV-C (μg/mL)
ACET group	Before treatment	9.27 ± 3.37	243.10 ± 83.42	186.49 ± 58.76	123.41 ± 24.26	130.63 ± 30.18
	After treatment	6.25 ± 2.20a	142.15 ± 61.50a	116.88 ± 42.52a	88.02 ± 16.65a	99.02 ± 27.52a
Control group	Before treatment	9.54 ± 3.42	228.49 ± 94.93	187.98 ± 74.09	130.97 ± 28.31	139.64 ± 34.72
	After treatment	8.28 ± 2.69b	190.02 ± 98.17b	146.45 ± 57.89b	112.05 ± 21.46b	120.02 ± 21.57b

^aP < 0.05, pre- vs post-treatment in the acupoint catgut embedding therapy (ACET) group.

^bP < 0.05, ACET vs control post-treatment.

LSM: Liver stiffness measurement; HA: Hyaluronic acid; LN: Laminin; PCIII: Type III procollagen; IV-C: Type IV collagen; ACET: Acupoint catgut embedding therapy.

Serum concentrations of PDGF, TGF-β1, and CK-18

Serum concentrations of PDGF, TGF-β1, and CK-18 are presented in Table 6. Baseline values were comparable between the groups (P > 0.05). Post-treatment, both groups exhibited significant reductions in PDGF, TGF-β1, and CK-18 levels (P < 0.05). Post-treatment comparison revealed that the ACET group achieved significantly lower levels of these biomarkers than the control group (P < 0.05).

Table 6 Serum platelet-derived growth factor, transforming growth factor-β1, and cytokeratin 18 level comparisons.

		PDGF (pg/mL)	TGF-β1 (pg/mL)	CK-18 (ng/mL)
ACET group	Before treatment	30.72 ± 8.14	43.22 ± 8.46	136.56 ± 12.76
	After treatment	15.25 ± 4.39a	32.14 ± 6.57a	109.88 ± 12.32a
Control group	Before treatment	28.54 ± 8.42	48.49 ± 8.93	130.97 ± 13.09
	After treatment	23.20 ± 5.67b	40.09 ± 8.03b	126.40 ± 11.84b

^aP < 0.05, pre- vs post-treatment in the acupoint catgut embedding therapy (ACET) group.

^bP < 0.05, ACET vs control post-treatment.

PDGF: Platelet-derived growth factor; TGF-β1: Transforming growth factor-β1; CK-18: Cytokeratin 18; ACET: Acupoint catgut embedding therapy.

DISCUSSION

MAFLD, previously referred to as nonalcoholic fatty liver disease[17], has experienced a marked increase in global incidence, reflecting changes in socioeconomic development and dietary patterns, with an emerging predilection among younger populations[18]. Current clinical priorities include the early detection of hepatic fibrosis, the identification of effective pharmacological interventions, and the prevention of disease progression in MAFLD-associated fibrosis[19]. Integrative strategies that combine TCM with Western medical approaches, particularly those that address individual constitutional predispositions, may offer improved therapeutic outcomes aligned with contemporary healthcare needs[20].

In TCM theory, MAFLD manifests through various syndrome patterns, including hypochondriac pain, abdominal distention and fullness, liver fixation, and dampness obstruction[21]. For acupoint selection, we focused on key back-shu points corresponding to visceral regulation, specifically Ganshu, Pishu, Weishu, and Shenshu[22,23]. As described in “Ling Shu • Wei Qi”, these back-shu points serve as convergence sites for abdominal qi, facilitating the transmission of zang-fu organ qi to the back through meridian pathways and enabling organ regulation through acupuncture stimulation[24]. Taichong, the source point of the Liver Meridian of Foot-Jueyin, exerts liver-soothing and qi-regulating effects[25]. Geshu, regarded as the influential point for blood disorders, effectively enhances blood flow and alleviates stasis through acupuncture stimulation[26]. Fenglong, a principal acupoint for phlegm-related conditions, promotes the resolution of turbidity, transformation of phlegm, and improvement of the transport function[27]. Zusanli contributes to dampness elimination and spleen reinforcement, thereby consolidating the postnatal constitution[28]. The combined application of these acupoints produces synergistic therapeutic effects, including hepatic regulation, splenic tonification, qi modulation, phlegm resolution, and stasis removal, to facilitate collateral unblocking. This study showed that the ACET group achieved superior overall therapeutic effectiveness compared to the control group, indicating enhanced therapeutic potential for MAFLD. ACET treatment resulted in significant improvements in BMI, AC, BW, TC, TG, ALT, and AST, both pre- and post-treatment (P < 0.05), with post-treatment gains exceeding those observed in the control group (P < 0.05). These findings indicate that ACET effectively promotes BW reduction in patients with MAFLD while significantly ameliorating lipid metabolism disorders and liver function impairment. This therapeutic approach simultaneously addresses internal pathophysiology and external clinical manifestations, modulating spleen-stomach function, promoting middle energizer circulation, and restoring qi–blood balance.

LSM demonstrates high diagnostic accuracy and sensitivity in assessing liver fibrosis and hepatic steatosis[29], while the liver fibrosis panel serves as a classical diagnostic biomarker for evaluating hepatofibrosis[30]. In this study, the ACET group exhibited statistically significant reductions in both LSM values and liver fibrosis-related indicators between the pre- and post-treatment periods (P < 0.05). Furthermore, post-treatment comparisons between the groups revealed significant differences in these parameters (P < 0.05). Collectively, these findings indicate the favorable clinical efficacy of both treatment approaches for managing MAFLD.

PDGF is recognized as one of the most potent mitogens for hepatic stellate cells (HSCs)[31]. TGF-β1 plays a crucial role in liver fibrosis by promoting HSC activation, inhibiting hepatocyte regeneration, and inducing hepatocyte apoptosis[32]. Additionally, TGF-β1 regulates various cellular processes, including growth, proliferation, differentiation, and migration[33]. CK-18, a major intermediate filament protein that constitutes the hepatocyte cytoskeleton, serves as a biomarker reflecting hepatocyte necrosis[34]. As an apoptotic product preceding massive hepatocyte necrosis, CK-18 expression levels directly correlate with the severity of liver damage, providing a valuable indicator for monitoring hepatic pathological changes and disease progression. In this study, the ACET group exhibited statistically significant reductions in PDGF, TGF-β1, and CK-18 levels from pre- to post-treatment. Furthermore, post-treatment comparisons between the groups revealed significantly lower levels in these biomarkers (P < 0.05). These findings suggest that the therapeutic effects of ACET in MAFLD may be mediated through modulation of HSC activation and hepatocyte apoptosis pathways.

This study has several limitations that warrant consideration. First, the absence of cellular-level analysis limits our understanding of the precise mechanisms through which ACET exerts therapeutic effects in MAFLD. Future studies should prioritize mechanistic explorations at the cellular and molecular levels. Second, the study did not assess the long-term prognostic impact of ACET on MAFLD; supplementary follow-up periods of 5 years or more are necessary to confirm its sustained clinical benefits. Finally, factors influencing treatment efficacy were not analyzed; incorporating such analyses in future research could help identify specific patient populations most likely to benefit from ACET.

CONCLUSION

In conclusion, ACET exhibits promising therapeutic effects in the management of MAFLD, possibly by modulating the activation of HSCs and hepatocyte apoptosis. Further research is warranted to elucidate the precise molecular and cellular pathways underlying these effects.