Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (2): 480-489.DOI: 10.19852/j.cnki.jtcm.20250821.001
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Tongue color tones in Traditional Chinese Medicine correlate with liver histology of metabolic dysfunction-associated steatohepatitis in morbidly obese patients undergoing metabolic and bariatric surgery
CEN Zhikang1, HUANG Bing1, ZHANG Pengfei1, LIU Dongyang1, MO Yanxin1, ZHU Fei1, FAN Mengqi2, NI Zheng1, XU Ying3, LIU Wei4, WU Shuduo5, XU Aimin6,7, SONG Erfei2,8(
), YE Dewei1()
- 1
Key Laboratory of Metabolic Phenotyping in Model Animals ,Guangdong Pharmaceutical University Guangzhou 510006, China
2Institute of Metabolic Science ,Science and Technology Innovation Center, Guangzhou University of Chinese Medicine Guangzhou 510006, China
3School of Chinese Medicine ,Guangdong Pharmaceutical University Guangzhou 510006, China
4the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510400, China
5Division of Hepatology ,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510120, China
6State Key Laboratory of Pharmaceutical Biotechnology ,the University of Hong Kong Hong Kong, China
7Department of Medicine ,The University of Hong Kong Hong Kong 999077, China
8Department of Bariatric Surgery ,the First Affiliated Hospital of Jinan University Guangzhou 510630, China
-
Received:2025-03-31Accepted:2025-06-21Online:2026-04-15Published:2025-08-21 -
Contact:YE Dewei, Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou 510006, China. dewei.ye@foxmail.com; Telephone: +86-20-39353115; SONG Erfei, Department of Bariatric Surgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China. songerfei@jnu.edu.cn; Telephone: +86-20-38688610 -
Supported by:Immunometabolism Mechanisms Underlying the Development of Chronic Diseases and Therapeutic Benefits of Traditional Chinese Medicine(2024ZD0521005);Functional Investigation of Proteinase 3 in the Development of Diabetic Kidney Diseases and Mechanistic Insights into Therapeutic Benefits of Traditional Chinese Medicine Formula(82374171);Exploration of Pathogenic Role of Neutrophil Extracellular Traps in Increased Susceptibility to Drug-induced Liver Injury under Co-existing Metabolic Dysfunction-associated Steatohepatitis(2024A1515012945);Basic and Translational Investigation of Immunometabolism in Metabolic Diseases(SL2023A04-J01031);Key Laboratory of Model Animal Phenotyping and Basic Research in Metabolic Diseases(2018KSYS003)
Cite this article
CEN Zhikang, HUANG Bing, ZHANG Pengfei, LIU Dongyang, MO Yanxin, ZHU Fei, FAN Mengqi, NI Zheng, XU Ying, LIU Wei, WU Shuduo, XU Aimin, SONG Erfei, YE Dewei. Tongue color tones in Traditional Chinese Medicine correlate with liver histology of metabolic dysfunction-associated steatohepatitis in morbidly obese patients undergoing metabolic and bariatric surgery[J]. Journal of Traditional Chinese Medicine, 2026, 46(2): 480-489.
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Table 1 Clinical and histological characteristics of participants
| Characteristic | All subjects | Steatosis | Lobular inflammation | |||
|---|---|---|---|---|---|---|
| No | Yes | No | Yes | |||
| Female [n (%)] | 39 (65) | 13 (92.86) | 26 (56.52) | 13 (86.67) | 26 (57.78) | |
| Male [n (%)] | 21 (35) | 1 (7.14) | 20 (43.48) | 2 (13.33) | 19 (42.22) | |
| Age [years, median (IQR)] | 31 (26, 36) | 31.5 (26.75, 33.75) | 31 (25.25, 37.5) | 32 (26, 34.5) | 31 (26, 36) | |
| Weight [kg, median (IQR)] | 113.15 (90.68, 127.58) | 91.25 (72.58, 101.23) | 116.85 (99.7, 131.78) | 95 (76.7, 106.25) | 116.5 (99.5, 131.4) | |
| BMI [kg/m2, median (IQR)] | 38.8 (33.5, 43.6) | 32.65 (30.3, 40.62) | 39.81 (36.34, 44.38) | 33.12 (31.12, 40.45) | 39.93 (36.1, 44.12) | |
| Waist circumference [cm, median (IQR)] | 119.5 (107.63, 131.88) | 106.1 (100.25, 110) | 124 (116.13, 135) | 108 (101, 114) | 124 (116, 135) | |
| ALT [U/L, median (IQR)] | 39 (20.25, 68.25) | 18.5 (16, 27) | 47.5 (32, 75.75) | 19 (16.5, 26) | 47 (32, 76) | |
| AST [U/L, median (IQR)] | 22 (17, 33) | 17 (13.25, 18.75) | 27 (20.25, 38) | 17 (14, 18.5) | 28 (21, 38) | |
| ALP [U/L, median (IQR)] | 80 (64.25, 96.75) | 64.5 (57.25, 85.5) | 83.5 (68.25, 99.5) | 63 (56, 82) | 84 (72, 98) | |
| γ-GT [U/L, median (IQR)] | 37 (23.25, 54) | 25 (17.25, 35.5) | 42 (25.5, 57.25) | 24 (16.5, 29) | 41 (27, 58) | |
| ADA [U/L, median (IQR)] | 12 (10, 14.75) | 10.5 (10, 12) | 12 (10.25, 15) | 10 (9, 12) | 12 (11, 15) | |
| Diabetes [n (%)] | 7 (11.67) | 1 (7.14) | 6 (13.04) | 1 (6.67) | 6 (13.33) | |
| Hypertension [n (%)] | 5 (8.33) | 0 (0) | 5 (10.87) | 0 (0) | 5 (11.11) | |
| TCHOL [mmol/L, median (IQR)] | 5.14 (4.56, 5.94) | 5.62 (4.28, 5.79) | 5.1 (4.8, 6.13) | 5.64 (4.21, 5.88) | 5.08 (4.78, 5.94) | |
| HDL-C [mmol/L, median (IQR)] | 1.02 (0.92, 1.21) | 1.31 (1.03, 1.43) | 0.99 (0.9, 1.12) | 1.3 (1.1, 1.4) | 0.99 (0.89, 1.09) | |
| LDL-C [mmol/L, median (IQR)] | 3.16 (2.7, 3.59) | 3.21 (2.48, 3.43) | 3.12 (2.79, 3.62) | 3.28 (2.54, 3.46) | 3.09 (2.75, 3.6) | |
| TG [mmol/L, median (IQR)] | 1.77 (1.11, 2.48) | 1.2 (1.04, 1.59) | 1.88 (1.38, 2.82) | 1.15 (1.05, 1.65) | 1.89 (1.34, 2.87) | |
| LDH [U/L, median (IQR)] | 201.5 (180.25, 231.5) | 188.5 (166.75, 197.25) | 210.5 (183.25, 238.75) | 193 (165.5, 205.5) | 206 (183, 235) | |
| Uric acid [μmol/L, median (IQR)] | 450.35 (387, 508.23) | 396 (363.75, 444.4) | 468.25 (422.25, 547.98) | 383.7 (364.5, 448.6) | 462.5 (426, 548) | |
| APOA [g/L, median (IQR)] | 1.3 (1.2, 1.39) | 1.37 (1.31, 1.47) | 1.27 (1.19, 1.36) | 1.36 (1.31, 1.44) | 1.26 (1.18, 1.36) | |
| APOB [g/L, median (IQR)] | 0.97 (0.8, 1.2) | 0.93 (0.75, 1.02) | 0.97 (0.83, 1.2) | 0.97 (0.78, 1.15) | 0.97 (0.83, 1.18) | |
| Fasting glucose [mmol/L, median (IQR)] | 5.58 (5.03, 7.02) | 5.1 (4.87, 6.06) | 5.67 (5.24, 7.78) | 5.1 (4.73, 5.92) | 5.68 (5.25, 8.02) | |
| HbA1c [%, median (IQR)] | 5.85 (5.5, 6.88) | 5.6 (5.33, 5.85) | 5.9 (5.6, 7.2) | 5.6 (5.25, 5.85) | 5.9 (5.6, 7.3) | |
| Insulin [mIU/L, median (IQR)] | 22.92 (12.72, 31.76) | 12.36 (10.42, 20.24) | 26.27 (15.77, 31.99) | 12.56 (10.88, 19.42) | 26.39 (15.58, 32.83) | |
| C-peptide [ng/mL, median (IQR)] | 3.68 (2.76, 4.87) | 2.81 (2.45, 3.15) | 4.06 (3.07, 5.12) | 2.77 (2.48, 3.12) | 4.2 (3.14, 5.2) | |
| Transferrin [g/L, median (IQR)] | 2.56 (2.24, 2.94) | 2.74 (2.27, 2.98) | 2.51 (2.24, 2.86) | 2.94 (2.29, 2.99) | 2.47 (2.24, 2.83) | |
| Hepatic steatosis ≥ 1 [n (%)] | 46 (76.67) | - | - | - | - | |
| Hepatocyte ballooning ≥ 1 [n (%)] | 20 (33.33) | - | - | - | - | |
| Lobular inflammation ≥ 1 [n (%)] | 45 (75) | - | - | - | - | |
| Fibrosis [n (%)] | 28 (46.67) | - | - | - | - | |
Table 1 Clinical and histological characteristics of participants
| Characteristic | All subjects | Steatosis | Lobular inflammation | |||
|---|---|---|---|---|---|---|
| No | Yes | No | Yes | |||
| Female [n (%)] | 39 (65) | 13 (92.86) | 26 (56.52) | 13 (86.67) | 26 (57.78) | |
| Male [n (%)] | 21 (35) | 1 (7.14) | 20 (43.48) | 2 (13.33) | 19 (42.22) | |
| Age [years, median (IQR)] | 31 (26, 36) | 31.5 (26.75, 33.75) | 31 (25.25, 37.5) | 32 (26, 34.5) | 31 (26, 36) | |
| Weight [kg, median (IQR)] | 113.15 (90.68, 127.58) | 91.25 (72.58, 101.23) | 116.85 (99.7, 131.78) | 95 (76.7, 106.25) | 116.5 (99.5, 131.4) | |
| BMI [kg/m2, median (IQR)] | 38.8 (33.5, 43.6) | 32.65 (30.3, 40.62) | 39.81 (36.34, 44.38) | 33.12 (31.12, 40.45) | 39.93 (36.1, 44.12) | |
| Waist circumference [cm, median (IQR)] | 119.5 (107.63, 131.88) | 106.1 (100.25, 110) | 124 (116.13, 135) | 108 (101, 114) | 124 (116, 135) | |
| ALT [U/L, median (IQR)] | 39 (20.25, 68.25) | 18.5 (16, 27) | 47.5 (32, 75.75) | 19 (16.5, 26) | 47 (32, 76) | |
| AST [U/L, median (IQR)] | 22 (17, 33) | 17 (13.25, 18.75) | 27 (20.25, 38) | 17 (14, 18.5) | 28 (21, 38) | |
| ALP [U/L, median (IQR)] | 80 (64.25, 96.75) | 64.5 (57.25, 85.5) | 83.5 (68.25, 99.5) | 63 (56, 82) | 84 (72, 98) | |
| γ-GT [U/L, median (IQR)] | 37 (23.25, 54) | 25 (17.25, 35.5) | 42 (25.5, 57.25) | 24 (16.5, 29) | 41 (27, 58) | |
| ADA [U/L, median (IQR)] | 12 (10, 14.75) | 10.5 (10, 12) | 12 (10.25, 15) | 10 (9, 12) | 12 (11, 15) | |
| Diabetes [n (%)] | 7 (11.67) | 1 (7.14) | 6 (13.04) | 1 (6.67) | 6 (13.33) | |
| Hypertension [n (%)] | 5 (8.33) | 0 (0) | 5 (10.87) | 0 (0) | 5 (11.11) | |
| TCHOL [mmol/L, median (IQR)] | 5.14 (4.56, 5.94) | 5.62 (4.28, 5.79) | 5.1 (4.8, 6.13) | 5.64 (4.21, 5.88) | 5.08 (4.78, 5.94) | |
| HDL-C [mmol/L, median (IQR)] | 1.02 (0.92, 1.21) | 1.31 (1.03, 1.43) | 0.99 (0.9, 1.12) | 1.3 (1.1, 1.4) | 0.99 (0.89, 1.09) | |
| LDL-C [mmol/L, median (IQR)] | 3.16 (2.7, 3.59) | 3.21 (2.48, 3.43) | 3.12 (2.79, 3.62) | 3.28 (2.54, 3.46) | 3.09 (2.75, 3.6) | |
| TG [mmol/L, median (IQR)] | 1.77 (1.11, 2.48) | 1.2 (1.04, 1.59) | 1.88 (1.38, 2.82) | 1.15 (1.05, 1.65) | 1.89 (1.34, 2.87) | |
| LDH [U/L, median (IQR)] | 201.5 (180.25, 231.5) | 188.5 (166.75, 197.25) | 210.5 (183.25, 238.75) | 193 (165.5, 205.5) | 206 (183, 235) | |
| Uric acid [μmol/L, median (IQR)] | 450.35 (387, 508.23) | 396 (363.75, 444.4) | 468.25 (422.25, 547.98) | 383.7 (364.5, 448.6) | 462.5 (426, 548) | |
| APOA [g/L, median (IQR)] | 1.3 (1.2, 1.39) | 1.37 (1.31, 1.47) | 1.27 (1.19, 1.36) | 1.36 (1.31, 1.44) | 1.26 (1.18, 1.36) | |
| APOB [g/L, median (IQR)] | 0.97 (0.8, 1.2) | 0.93 (0.75, 1.02) | 0.97 (0.83, 1.2) | 0.97 (0.78, 1.15) | 0.97 (0.83, 1.18) | |
| Fasting glucose [mmol/L, median (IQR)] | 5.58 (5.03, 7.02) | 5.1 (4.87, 6.06) | 5.67 (5.24, 7.78) | 5.1 (4.73, 5.92) | 5.68 (5.25, 8.02) | |
| HbA1c [%, median (IQR)] | 5.85 (5.5, 6.88) | 5.6 (5.33, 5.85) | 5.9 (5.6, 7.2) | 5.6 (5.25, 5.85) | 5.9 (5.6, 7.3) | |
| Insulin [mIU/L, median (IQR)] | 22.92 (12.72, 31.76) | 12.36 (10.42, 20.24) | 26.27 (15.77, 31.99) | 12.56 (10.88, 19.42) | 26.39 (15.58, 32.83) | |
| C-peptide [ng/mL, median (IQR)] | 3.68 (2.76, 4.87) | 2.81 (2.45, 3.15) | 4.06 (3.07, 5.12) | 2.77 (2.48, 3.12) | 4.2 (3.14, 5.2) | |
| Transferrin [g/L, median (IQR)] | 2.56 (2.24, 2.94) | 2.74 (2.27, 2.98) | 2.51 (2.24, 2.86) | 2.94 (2.29, 2.99) | 2.47 (2.24, 2.83) | |
| Hepatic steatosis ≥ 1 [n (%)] | 46 (76.67) | - | - | - | - | |
| Hepatocyte ballooning ≥ 1 [n (%)] | 20 (33.33) | - | - | - | - | |
| Lobular inflammation ≥ 1 [n (%)] | 45 (75) | - | - | - | - | |
| Fibrosis [n (%)] | 28 (46.67) | - | - | - | - | |
Figure 1 Color tones in distinct zones in the tongue correlated with histological features of MASH in liver biopsy and biochemical parameters A: heat map showing the results of correlation analysis of MASH-specific features (including steatosis, lobular inflammation, hepatocyte ballooning, and NASH CRN scores) with RGB values measured in the tongue tip; B: heat map of MASH-specific features with RGB values measured in tongue coating; C: heat map of correlation analysis of MASH-specific features with RGB values measured in the tongue edge; D: correlation analysis of yellow values in tongue coating with blood levels of ALT in heat-syndrome subgroup; E: correlation analysis of yellow values in tongue coating with blood levels of lipoprotein (a) in heat-syndrome subgroup; F: correlation analysis of yellow values in tongue coating with blood levels of vitamin B1 in heat-syndrome subgroup. NASH CRN: non-alcoholic steatohepatitis clinical research network; ALT: alanine aminotransferase; MASH: metabolic dysfunction-associated steatohepatitis; RGB: red, green, and blue. Statistical analyses were performed using Spearman correlation analysis (panels A-C, n = 60) and Pearson correlation analysis (panels D-F, n = 20).
Figure 1 Color tones in distinct zones in the tongue correlated with histological features of MASH in liver biopsy and biochemical parameters A: heat map showing the results of correlation analysis of MASH-specific features (including steatosis, lobular inflammation, hepatocyte ballooning, and NASH CRN scores) with RGB values measured in the tongue tip; B: heat map of MASH-specific features with RGB values measured in tongue coating; C: heat map of correlation analysis of MASH-specific features with RGB values measured in the tongue edge; D: correlation analysis of yellow values in tongue coating with blood levels of ALT in heat-syndrome subgroup; E: correlation analysis of yellow values in tongue coating with blood levels of lipoprotein (a) in heat-syndrome subgroup; F: correlation analysis of yellow values in tongue coating with blood levels of vitamin B1 in heat-syndrome subgroup. NASH CRN: non-alcoholic steatohepatitis clinical research network; ALT: alanine aminotransferase; MASH: metabolic dysfunction-associated steatohepatitis; RGB: red, green, and blue. Statistical analyses were performed using Spearman correlation analysis (panels A-C, n = 60) and Pearson correlation analysis (panels D-F, n = 20).
Figure 2 Analysis of RGB values in distinct zones of the tongue in patients with or without histological feature of steatosis in liver biopsies A: values of R, G, and B channels in the zone of tongue tip in subgroup of patients with or without steatosis in liver biopsies; B: values of R, G, and B channels in the zone of tongue coating in subgroup of patients with or without steatosis in liver biopsies; C: values of R, G, and B channels in the zone of tongue edge in subgroup of patients with or without steatosis in liver biopsies. No Steatosis group: absence of significant hepatic steatosis (< 5%) by histology. Steatosis group: presence of ≥ 5% hepatic steatosis by histology. RGB: red, green, and blue. Statistical analyses were measured using one-way analysis of variance for multiple comparisons Data are expressed as mean ± standard deviation (no steatosis: n = 14; steatosis: n = 46). aP < 0.05 and bP < 0.01 vs no steatosis group.
Figure 2 Analysis of RGB values in distinct zones of the tongue in patients with or without histological feature of steatosis in liver biopsies A: values of R, G, and B channels in the zone of tongue tip in subgroup of patients with or without steatosis in liver biopsies; B: values of R, G, and B channels in the zone of tongue coating in subgroup of patients with or without steatosis in liver biopsies; C: values of R, G, and B channels in the zone of tongue edge in subgroup of patients with or without steatosis in liver biopsies. No Steatosis group: absence of significant hepatic steatosis (< 5%) by histology. Steatosis group: presence of ≥ 5% hepatic steatosis by histology. RGB: red, green, and blue. Statistical analyses were measured using one-way analysis of variance for multiple comparisons Data are expressed as mean ± standard deviation (no steatosis: n = 14; steatosis: n = 46). aP < 0.05 and bP < 0.01 vs no steatosis group.
Figure 3 RGB values in tongue edge exhibited a step-wise increase in association with histological grading of MASH in liver biopsies A: values in the channel of R in patients with steatosis score 0, 1, 2, and 3; B: values in the channel of G in patients with steatosis score 0, 1, 2, and 3; C: values in the channel of B in patients with steatosis score 0, 1, 2, and 3; D: values in the channel of R in patients with histological score 0, 1, and 2 of lobular inflammation; E: values in the channel of G in patients with histological score 0, 1, and 2 of lobular inflammation; F: values in the channel of B in patients with histological score 0, 1, and 2 of lobular inflammation; G: values in the channel of R in patients with NASH CRN score 0 to 6; H: values in the channel of G in patients with NASH CRN score 0 to 6; I: values in the channel of B in patients with NASH CRN score 0 to 6. R: red; G: green; B: blue; NASH CRN: non-alcoholic steatohepatitis clinical research network; MASH: metabolic dysfunction-associated steatohepatitis. Statistical analyses were performed using Spearman correlation analysis (n = 60).
Figure 3 RGB values in tongue edge exhibited a step-wise increase in association with histological grading of MASH in liver biopsies A: values in the channel of R in patients with steatosis score 0, 1, 2, and 3; B: values in the channel of G in patients with steatosis score 0, 1, 2, and 3; C: values in the channel of B in patients with steatosis score 0, 1, 2, and 3; D: values in the channel of R in patients with histological score 0, 1, and 2 of lobular inflammation; E: values in the channel of G in patients with histological score 0, 1, and 2 of lobular inflammation; F: values in the channel of B in patients with histological score 0, 1, and 2 of lobular inflammation; G: values in the channel of R in patients with NASH CRN score 0 to 6; H: values in the channel of G in patients with NASH CRN score 0 to 6; I: values in the channel of B in patients with NASH CRN score 0 to 6. R: red; G: green; B: blue; NASH CRN: non-alcoholic steatohepatitis clinical research network; MASH: metabolic dysfunction-associated steatohepatitis. Statistical analyses were performed using Spearman correlation analysis (n = 60).
Figure 4 Interaction analysis reveals the distribution of histological features of MASH in patients with or without tooth-sign in tongue A: the distribution and percentage of patients with or without histological feature steatosis in patients with or without tooth-sign in tongue; B: the distribution and percentage of patients with or without histological feature lobular inflammation in patients with or without tooth-sign in tongue; C: the distribution and percentage of patients with or without histological feature hepatocyte ballooning in patients with or without tooth-sign in tongue; D: the distribution and percentage of patients with or without histological feature liver fibrosis in patients with or without tooth-sign in tongue. MASH: metabolic dysfunction-associated steatohepatitis. Statistical analyses were performed using the χ 2 test (n = 60).
Figure 4 Interaction analysis reveals the distribution of histological features of MASH in patients with or without tooth-sign in tongue A: the distribution and percentage of patients with or without histological feature steatosis in patients with or without tooth-sign in tongue; B: the distribution and percentage of patients with or without histological feature lobular inflammation in patients with or without tooth-sign in tongue; C: the distribution and percentage of patients with or without histological feature hepatocyte ballooning in patients with or without tooth-sign in tongue; D: the distribution and percentage of patients with or without histological feature liver fibrosis in patients with or without tooth-sign in tongue. MASH: metabolic dysfunction-associated steatohepatitis. Statistical analyses were performed using the χ 2 test (n = 60).
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