Published online May 21, 2026. doi: 10.3748/wjg.v32.i19.116513
Revised: January 13, 2026
Accepted: February 26, 2026
Published online: May 21, 2026
Processing time: 186 Days and 20 Hours
Real-world data remain limited on the effectiveness of magnesium isoglycyr
To evaluate the prophylactic and therapeutic effectiveness of MgIG for hepatic injury in patients undergoing hepatectomy in a real-world setting.
We retrospectively reviewed the clinical data of consecutive Chinese patients who underwent hepatectomy between March 2020 and March 2023 at two tertiary care hospitals in China. The cohorts were balanced using propensity score matching (PSM). The primary outcome was the prevalence of postoperative liver injury, defined as ≥ 3 × upper limit of normal of the serum levels of alanine aminotransferase (ALT) or aspartate aminotransferase.
The rate of postoperative liver injury was 76.9% among 1711 eligible patients. After PSM, patients who received perioperative MgIG had a significantly greater reduction in the prevalence of liver injuries than those who only received postoperative MgIG on postoperative day (POD) 3 (53.3% vs 69.1%; P = 0.006) and POD 7 (14.2% vs 23.6%; P = 0.027). The proportions of patients with ≥ 50% reduction in ALT were significantly higher in patients treated with MgIG plus other liver protectants than those treated with other liver protectants on POD 3 and 7, and upon hospital discharge. Multivariable analysis indicated an independent protective role of prophylactic MgIG in postoperative liver injury.
This study indicates that the addition of preoperative prophylaxis to postoperative treatment with MgIG can mitigate of the rise of aminotransferases and enhance postoperative liver function recovery, conferring benefits on more surgical patients.
Core Tip: In this real-world study of 1711 patients undergoing hepatectomy, magnesium isoglycyrrhizinate demonstrated meaningful benefits in preventing and treating postoperative hepatic injuries. Perioperative magnesium isoglycyrrhizinate significantly reduced the incidence of liver injury and accelerated postoperative liver function recovery vs postoperative use alone. The patients in the prophylaxis group had significantly lower alanine aminotransferase levels on postoperative day 1 compared to the non-prophylaxis group. Even without prophylaxis, postoperative magnesium isoglycyrrhizinate was also associated with higher rates of alanine aminotransferase improvement. Multivariable analysis confirmed its independent protective effect. These findings suggest that adding preoperative magnesium isoglycyrrhizinate prophylaxis enhances postoperative hepatic recovery and benefits a broader surgical population.
- Citation: Xie ZQ, Wei JX, Zhong JY, Luo X, Zhuang HK, Ma XW, Wang QB, Tan WL, Wang BK, Chen YJ, Li CJ, Shang CZ. Effectiveness of magnesium isoglycyrrhizinate on perioperative hepatic function protection in patients undergoing hepatectomy. World J Gastroenterol 2026; 32(19): 116513
- URL: https://www.wjgnet.com/1007-9327/full/v32/i19/116513.htm
- DOI: https://dx.doi.org/10.3748/wjg.v32.i19.116513
Hepatectomy remains a major therapeutic modality for primary or secondary liver tumors and benign or malignant biliary diseases but incurs significant morbidity, including postoperative liver failure, and mortality of surgical patients[1-4]. The rate of postoperative morbidity was reported to be 15.6% in 793 consecutive patients undergoing hepatectomy at a tertiary care institution by Kamiyama et al[4] and 45% in 1803 consecutive cases undergoing hepatic resection at Memorial Sloan-Kettering Cancer Center by Jarnagin et al[5]. Perioperative liver impairment and injury remain a serious concern of hepatectomy and significantly contribute to complications of hepatectomy. According to Kauffmann and Fong[6] amelioration of perioperative liver function and enhancing liver function recovery after hepatectomy remains a research focus for the preceding decades.
Inflammation is a central driver of the initiation and progression of virtually all forms of liver disease, and progressive inflammatory injury can ultimately lead to cirrhosis, hepatocellular carcinoma, and other end-stage hepatic conditions. Preventative strategies such as preoperative pharmacotherapy with tumor necrosis factor-α inhibitor pentoxifylline have been attempted for perioperative liver protection for enhanced functional recovery following hepatectomy[7-9]. Glycyrrhizic acid is a principal active ingredient of Chinese medicinal herb Glycyrrhizae Radix et Rhizoma and has multiple biological activities including immune modulatory, antioxidant, anti-inflammatory and hepatoprotective activities[10,11]. Magnesium isoglycyrrhizinate, a fourth generation glycyrrhizic acid preparation, is a magnesium salt mainly consisting of 18α-glycyrrhizic acid stereoisomers. It has been shown to modulate several canonical inflammatory pathways, including the phospholipase A2/arachidonic acid cascade, the nuclear factor kappa-B pathway, the mitogen-activated protein kinase/activator protein-1 pathway, and the signal transducer and activator of transcription 3 signaling axis. Through these mechanisms, it exerts potent antiinflammatory effects and has demonstrated clinical utility across a range of liver diseases, including viral hepatitis, drug-induced liver injury, fatty liver disease, perioperative hepatic injury, cirrhosis, and hepatocellular carcinoma[12-21] and has been incorporated into multiple national clinical practice guide
This real-world study across China sought to analyze the effectiveness of magnesium isoglycyrrhizinate for hepatoprotection in the perioperative period in patients undergoing hepatobiliary surgery. By leveraging data from more than one thousand patients, our findings provide additional real-world evidence supporting the role of magnesium isoglycyrrhizinate in reducing postoperative liver injury.
This retrospective, non-interventional cohort study included adult patients (≥ 18 years old) who underwent hepatectomy and received preoperative prophylaxis and/or postoperative treatment with magnesium isoglycyrrhizinate and/or other liver protectants at the Departments of Hepatobiliary Surgery at two tertiary care centers in China. Patients who had normal hepatic function [ALT/aspartate aminotransferase (AST) ≤ upper limit of normal (ULN)] within 3 days of surgery were eligible. Patients who had received liver protectants other than or in combination with magnesium isoglycyrrhizinate within 3 days of surgery were excluded. Patients with incomplete data were also excluded. Other exclusion criteria were abnormal renal function (serum blood urea nitrogen and creatinine > ULN), electrolyte disturbances, severe cardiovascular and central nervous system abnormalities, or end-stage cancer. Consecutive patients with abnormal liver function (ALT and AST) post hepatectomy who were treated with magnesium isoglycyrrhizinate and/or other liver protectants for at least 7 days were further analyzed. The data, including patient demographics and baseline characteristics, preoperative and postoperative serum levels of ALT and AST, extent of resection and length of hospitalization were collected from the electronic medical records systems of participating centers. All study data were obtained based on clinical, laboratory, and diagnostic assessments conducted during routine clinical practice at the participating centers and at the indicated timepoints postoperatively between March 2020 and March 2023.
The study protocol was approved by the local ethics committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (No. SYSKY-2023-1199-01). Patient consent was not required given the retrospective nature of the study. Protocols, data storage, and data use were compliant with international data privacy laws. All patients provided written informed consent for surgery.
A total of 876 patients in group A0 initiated magnesium isoglycyrrhizinate prophylaxis within 3 days before surgery; among them, 863 (group A2) had postoperative abnormal liver function; 75 of them (group A2-1) received postoperative magnesium isoglycyrrhizinate only and 532 (group A2-2) received postoperative magnesium isoglycyrrhizinate in combination with other liver protectants. Furthermore, 835 patients in group B0 did not receive any prophylactic hepatoprotective medication before surgery. Among them, 830 (group B2) had postoperative abnormal liver function; 5 of them (group B2-1) received postoperative magnesium isoglycyrrhizinate only, 110 (group B2-2) received postoperative magnesium isoglycyrrhizinate in combination with other liver protectants, 536 (group B2-3) received postoperative liver protectants excluding magnesium isoglycyrrhizinate, 30 (group B2-4) received no postoperative hepatoprotective treatment. Specifically, postoperative day (POD) 1 referred to the first calendar day after surgery. The median dose of magnesium isoglycyrrhizinate was 150 mg [interquartile range (IQR): 150-150] were given once daily in both the perioperative group (A2-2) and the postoperative group (B2-2). The duration of magnesium isoglycyrrhizinate treatment was 8.0 days (IQR: 8.0-11.0) and 8.0 days (IQR: 7.0-10.8) in the perioperative group (A2-2) and the postoperative group (B2-2), respectively. Other liver protectants mainly included glutathione, polyenes and butane-1,4-disulfonate.
The primary outcome of this study was the incidence of post hepatectomy hepatic injury, defined as ≥ 3 × ULN of the serum levels of ALT or AST. Key secondary outcomes included the changes from baseline in the serum levels of ALT and AST in patients who received perioperative vs those who received postoperative magnesium isoglycyrrhizinate, patients who received prophylaxis with magnesium isoglycyrrhizinate vs those who received no prophylaxis, and patients who were treated with magnesium isoglycyrrhizinate plus other liver protectants vs those treated with other liver protectants only, the proportions of patients treated with magnesium isoglycyrrhizinate plus other liver protectants vs those treated with other liver protectants only who achieved a ≥ 50% reduction from baseline in the serum levels of ALT and AST, and the rate of hepatic injury recovery, defined as return of serum levels of ALT and AST below ULN.
The sample size was determined by data availability. To assess whether the available sample size would provide adequate statistical power, we assumed a clinically meaningful effect size with an expected incidence of liver injury of 80% in the control group and 68% in the magnesium isoglycyrrhizinate group. With a two-sided α level of 0.05, a power of 80% (1-β), and equal allocation between groups (1:1), the required sample size was calculated to be 105 patients per group. The actual sample sizes in each group (A0: n = 876; B0: n = 835; A2-2: n = 532; B2-2: n = 110; B2-3: n = 536) substantially exceeded the calculated minimum requirement, ensuring adequate statistical power for the analyses.
Categorical variables were expressed as n (%). Continuous parameters were expressed as median and IQR. Cohorts were balanced by using the MatchIt function in the R software package for four clinically relevant prognostic outcome parameters including age, sex, ALT levels, and extent of resection as baseline characteristics (covariates). The resulting primary analysis sets included all patients who met the eligibility criteria and matched in the four covariates. Using nearest neighbor 1:1 or 1:3 matching, with a caliper of width equal to 0.02, patients who received magnesium isoglycyrrhizinate prophylaxis and postoperative treatment with magnesium isoglycyrrhizinate plus other liver protectants were matched 3:1 to patients who only received postoperative treatment with magnesium isoglycyrrhizinate plus other liver protectants. In addition, patients receiving no prophylaxis were matched 1:1 to patients who received magnesium isoglycyrrhizinate for prophylaxis, and patients receiving postoperative treatment with magnesium isoglycyrrhizinate plus other liver protectants were matched 1:3 to patients who were treated with other liver protectants only. Covariate balance after matching was assessed using standardized mean differences, with values < 0.1 indicating adequate balance.
Intergroup comparison was done using Student t test for normally distributed variables and Wilcoxon rank sum test for non-normally distributed variables. χ2 or Fisher’s exact test was used to compare categorical variables between groups where appropriate. The prevalence of hepatic injury was repeated measurements and after the raw data were stan
Additionally, a univariable analysis was initially performed, followed by a multivariable logistic regression, to investigate the association between potential factors and the prevalence of postoperative liver injury. Variables demonstrating a P value of less than 0.1 in the univariable logistic regression were included in the multivariable model. A P value < 0.05 (2-sided) was considered statistically significant.
The study flowchart was shown in Figure 1. Between March 2020 and March 2023, of 86455 patients with hospitalization records at the participating hospitals and screened for eligibility, 1711 consecutive patients who underwent hepatectomy were included in this retrospective analysis. The demographic and baseline characteristics are described in Table 1. Among them, 876 patients received preoperative prophylaxis with magnesium isoglycyrrhizinate, hereafter referred to as the prophylaxis group, and 835 did not, hereafter referred to as the non-prophylaxis group. Their median age was 54 years and 45.7% were male. The median ALT level was 23.0 U/L (IQR: 16.0-33.0 U/L) and the median AST level was 22.0 U/L (IQR: 17.0-29.0 U/L). Over half of the patients (55.1%) underwent major hepatectomy and 44.9% had minor hepatectomy. Baseline data of the extent of liver resection are provided at Supplementary Table 1.
| Characteristic | n = 1711 |
| Median age (IQR), years | 54.0 (46.0-62.0) |
| Sex | |
| Male | 781 (45.7) |
| Female | 930 (54.4) |
| Comorbidities | |
| Hypertension | 254 (14.9) |
| Diabetes | 142 (8.3) |
| Hyperlipidemia | 29 (1.7) |
| Coronary heart disease | 12 (0.7) |
| Smoking | |
| Yes | 411 (24.0) |
| No | 1300 (76.0) |
| Drinking | |
| Yes | 257 (15.0) |
| No | 1454 (85.0) |
| Preoperative liver biochemistry, median (IQR) | |
| Alanine aminotransferase, U/L | 23.0 (16.0-33.0) |
| Aspartate aminotransferase, U/L1 | 22.0 (17.0-29.0) |
| Total bilirubin, mg/dL2 | 12.0 (9.1-15.7) |
| Alkaline phosphatase, U/L3 | 76.0 (61.0-96.0) |
| Extent of resection | |
| Major resection | 942 (55.1) |
| Minor resection | 769 (44.9) |
Five hundred thirty-two patients in the prophylaxis group and 110 in the non-prophylaxis group were treated with magnesium isoglycyrrhizinate plus other liver protectants, hereafter referred to as perioperative magnesium isoglycyrrhizinate and postoperative magnesium isoglycyrrhizinate, respectively. After propensity score matching (PSM) (3:1) for 4 clinically relevant variables, 330 patients in the perioperative magnesium isoglycyrrhizinate group were matched to 110 in the postoperative magnesium isoglycyrrhizinate group (Table 2).
| Perioperative vs postoperative treatment | Before PSM | Statistical volume | P value | After PSM (3:1) | Statistical volume | P value | ||
| Perioperative treatment (n = 532) | Postoperative treatment (n = 110) | Perioperative treatment (n = 330) | Postoperative treatment (n = 110) | |||||
| Age, years, median (IQR) | 54.0 (47.0-62.0) | 54.0 (47.0-62.8) | W = 28311.0 | 0.592 | 54.0 (47.0-62.0) | 54.0 (47.0-62.8) | W = 17514.5 | 0.582 |
| Male sex | 280 (52.6) | 70 (63.6) | χ2 = 4.452 | 0.035 | 216 (65.5) | 70 (63.6) | χ2 = 0.120 | 0.729 |
| ALT, median (IQR) | 24.0 (17.0-33.0) | 31.00 (20.3-35.0) | W = 23603.5 | 0.001 | 31.0 (20.0-36.0) | 31.0 (20.3-35.0) | W = 18114.5 | 0.976 |
| Extent of resection | χ2 = 0.068 | 0.794 | χ2 = 0.003 | 0.953 | ||||
| Major resection | 351 (66.0) | 74 (67.3) | 223 (67.6) | 74 (67.3) | ||||
| Minor resection | 181 (34.0) | 36 (32.7) | 107 (32.4) | 36 (32.7) | ||||
| Prophylaxis vs no prophylaxis | Before PSM | Statistical volume | P value | After PSM (1:1) | Statistical volume | P value | ||
| Prophylaxis (n = 876) | No prophylaxis (n = 835) | Prophylaxis (n = 680) | No prophylaxis (n = 680) | |||||
| Age, years, median (IQR) | 53.5 (46.0-62.0) | 54.0 (46.0-62.0) | W = 359007.5 | 0.510 | 54.0 (46.8-62.0) | 53.0 (45.0-62.0) | W = 233831.0 | 0.716 |
| Male sex | 330 (37.7) | 451 (54.0) | χ2 = 46.01 | < 0.001 | 319 (46.9) | 321 (47.2) | χ2 = 0.012 | 0.913 |
| ALT, median (IQR) | 23.0 (16.0-33.0) | 24.00 (16.0-33.0) | W = 356161.5 | 0.349 | 23.0 (15.0-33.0) | 24.0 (16.0-33.0) | W = 228588.5 | 0.718 |
| Extent of resection | χ2 = 33.227 | < 0.001 | χ2 = 1.196 | 0.274 | ||||
| Major resection | 423 (48.3) | 519 (62.2) | 373 (54.9) | 393 (57.8) | ||||
| Minor resection | 453 (51.7) | 316 (37.8) | 307 (45.2) | 287 (42.2) | ||||
| Treatment with magnesium isoglycyrrhizinate plus other liver protectants vs other liver protectants only | Before PSM | Statistical volume | P value | After PSM (1:3) | Statistical volume | P value | ||
| MgIG plus other liver protectants (n = 110) | Other liver protectants (n = 536) | MgIG plus other liver protectants (n = 110) | Other liver protectants (n = 330) | |||||
| Age, years, median (IQR) | 54.0 (47.0-62.8) | 54.0 (47.0-62.0) | W = 28753.0 | 0.684 | 54.0 (47.0-62.8) | 54.0 (48.0-62.0) | W = 17948.0 | 0.861 |
| Male sex | 70 (63.6) | 342 (63.8) | χ2 = 0.001 | 0.973 | 70 (63.6) | 192 (58.2) | χ2 = 1.019 | 0.313 |
| ALT, median (IQR) | 204.5 (141.3-428.3) | 216.5 (116.8-384.0) | W = 28763.5 | 0.688 | W = 17186.0 | 0.404 | ||
| Extent of resection | χ2 = 1.264 | 0.261 | χ2 = 0.165 | 0.685 | ||||
| Major resection | 74 (67.3) | 389 (72.6) | 74 (67.3) | 215 (65.2) | ||||
| Minor resection | 36 (32.7) | 147 (27.4) | 36 (32.7) | 115 (34.9) | ||||
The proportion of patients with postoperative liver injury was significantly lower on POD 3 (53.3% vs 69.1%, P = 0.006) and POD 7 (14.2% vs 23.6%, P = 0.027) in patients who received perioperative magnesium isoglycyrrhizinate than those who received postoperative magnesium isoglycyrrhizinate only (Figure 2A). Patients who received perioperative magnesium isoglycyrrhizinate had significantly lower median levels of ALT on POD 3 (146.0 U/L, IQR: 64.0-251.0 U/L vs 166.5 U/L, IQR: 109.0-315.8 U/L, P = 0.013) and POD 7 (54.5 U/L, IQR: 42.0-86.0 U/L vs 72.0 U/L, IQR: 42.5-112.0 U/L, P = 0.022) than those who only received postoperative magnesium isoglycyrrhizinate (Figure 2B). Moreover, a significantly smaller rise from baseline in median ALT levels on POD 3 (118.0 U/L, IQR: 36.0-220.0 U/L vs 144.0 U/L, IQR: 82.5-279.0 U/L, P = 0.012) and POD 7 (27.0 U/L, IQR: 10.0-61.8 U/L vs 45.0 U/L, IQR: 20.0-83.0 U/L, P = 0.008) was observed in patients who received perioperative magnesium isoglycyrrhizinate than those who only received postoperative magnesium isoglycyrrhizinate, translating into a median 4.6-fold rise (IQR: 1.5-8.4) on POD 3 from baseline as compared with a median 6.1-fold rise with no prophylaxis (IQR: 2.8-12.4) (P = 0.011), and a median 1.1-fold rise (IQR: 0.4-2.7) on POD 7 as compared with 1.8-fold rise with no prophylaxis (IQR: 0.8-3.4) (P = 0.012) (Figure 2C and D). Similar findings were observed with changes in AST levels on POD 3 (Figure 2E-G).
Moreover, the analysis of changes in the prevalence of hepatic injury post hepatectomy by GEE showed a significant reduction on POD 3 and 7, and upon discharge vs POD 1 in patients who received perioperative magnesium isoglycyrrhizinate while there was a significant reduction in the prevalence of hepatic injury on POD 7 and upon discharge in patients who received postoperative magnesium isoglycyrrhizinate (Table 3 and Figure 3A). On POD 3 and 7, perioperative magnesium isoglycyrrhizinate was associated with a 53% (OR = 0.47, 95%CI: 0.29-0.79) and 45% (OR = 0.55, 95%CI: 0.32-0.94) reduction in the risk of hepatic injury, respectively, vs postoperative magnesium isoglycyrrhizinate.
| Estimates (SE) | Lower limit, upper limit | Z value | P value | OR (95%CI) | |
| Perioperative vs postoperative treatment | |||||
| POD 1 | -0.34 (0.32) | -0.97, 0.29 | -1.05 | 0.294 | 0.71 (0.38-1.34) |
| POD 3 | -0.75 (0.26) | -1.25, -0.24 | -2.88 | 0.004 | 0.47 (0.29-0.79) |
| POD 7 | -0.60 (0.28) | -1.14, -0.06 | -2.18 | 0.030 | 0.55 (0.32-0.94) |
| Discharge from hospital | 0.14 (0.36) | -0.58, 0.85 | 0.38 | 0.705 | 1.15 (0.56-2.34) |
| Postoperative treatment | |||||
| POD 3 vs POD 1 | -0.77 (0.26) | -1.29, -0.25 | -2.92 | 0.004 | 0.46 (0.28-0.78) |
| POD 7 vs POD 1 | -3.00 (0.34) | -3.67, -2.35 | -8.96 | < 0.001 | 0.05 (0.03-0.10) |
| Discharge vs POD 1 | -4.08 (0.40) | -4.86, -3.29 | -10.20 | < 0.001 | 0.02 (0.01-0.04) |
| Perioperative treatment | |||||
| POD 3 vs POD 1 | -1.18 (0.14) | -1.46, -0.91 | -8.41 | < 0.001 | 0.31 (0.23-0.40) |
| POD 7 vs POD 1 | -3.27 (0.20) | -3.66, -2.88 | -16.47 | < 0.001 | 0.04 (0.03-0.06) |
| Discharge vs POD 1 | -3.60 (0.21) | -4.01, -3.19 | -17.17 | < 0.001 | 0.03 (0.02-0.04) |
Furthermore, univariable and multivariable logistic regression analysis indicated that patients who received perioperative magnesium isoglycyrrhizinate was associated with a significant reduction of liver injury on POD 3 and POD 7 compared to those who only received postoperative magnesium isoglycyrrhizinate (POD 3: OR = 0.48, 95%CI: 0.29-0.81; POD 7: OR = 0.53, 95%CI: 0.31-0.92) (Supplementary Tables 2 and 3).
A sensitivity analysis excluding 84 patients whose ALT or AST follow-up was shorter than 7 days and patients with ALT or AST outlier values showed that the direction and significance of the between-group differences in liver injury risk on POD 3 and POD 7 remained consistent, supporting the stability of the main results. Perioperative magnesium isoglycyrrhizinate significantly reduced the incidence of postoperative liver injury on POD 3 (58.9% vs 75.3%; P = 0.005) and POD 7 (17.1% vs 26.9%; P = 0.042) compared to postoperative magnesium isoglycyrrhizinate (Supplementary Table 4).
We further performed a stratified analysis according to the extent of hepatectomy (minor vs major resection) to evaluate whether magnesium isoglycyrrhizinate modified the risk of postoperative liver injury. Across both subgroups, perioperative magnesium isoglycyrrhizinate showed a consistent trend toward reduced postoperative liver injury. Among patients undergoing major resection, perioperative magnesium isoglycyrrhizinate significantly lowered the incidence of liver injury on POD 3 (61.1% vs 77.1%; P = 0.025). By POD 7, however, the between-group difference was no longer statistically significant (20.0% vs 27.9%; P = 0.202) (Supplementary Table 5). In the minor resection subgroup, the incidence of liver injury also favored perioperative magnesium isoglycyrrhizinate vs postoperative magnesium isoglycyrrhizinate on both POD 3 (54.6% vs 71.9%; P = 0.088) and POD 7 (11.4% vs 25.0%; P = 0.083) although neither comparison reached statistical significance, likely due to the smaller sample size in this subgroup (Supplementary Table 5).
A total of 680 patients in the preoperative magnesium isoglycyrrhizinate prophylaxis group were matched 1:1 to 680 patients in the non-prophylaxis group (Table 2). The PSM patients in the prophylaxis group had significantly lower median ALT levels on POD 1 (197.5 U/L, IQR: 95.0-352.0 U/L vs 211.0 U/L, IQR: 109.0-387.0 U/L, P < 0.001), with a significantly smaller median rise from baseline in ALT levels compared to the non-prophylaxis group (171.50 U/L, IQR: 71.8-328.3 U/L vs 185.5 U/L, IQR: 93.8-362.8 U/L, Wilcoxon rank sum test, P < 0.001) (Figure 3B and C). This represented an 8.2-fold rise (IQR: 3.4-16.2) over baseline in the prophylaxis group vs a 9.9-fold increase (IQR: 4.1-19.8) in the non-prophylaxis group (P < 0.001) (Figure 3D). Similar findings were observed with AST levels on POD 1 (Figure 3B-D).
Furthermore, univariable and multivariable logistic regression analysis indicated that patients who received preoperative magnesium isoglycyrrhizinate was associated with a 24% reduced risk of postoperative liver injury compared to those in the non-prophylaxis group (OR = 0.76, 95%CI: 0.58-0.98) (Supplementary Table 6).
Postoperative abnormal liver function was documented in 681 hospitalization records of patients who received no preoperative magnesium isoglycyrrhizinate prophylaxis; 110 of them were treated with magnesium isoglycyrrhizinate plus other liver protectants and 536 were treated with other liver protectants only and they were matched 1:3 for further analysis (Table 2). The proportions of patients with ≥ 50% reduction in the serum levels of ALT and AST or normalized levels of ALT and AST (≤ ULN) steadily increased post hepatectomy in both patients treated with magnesium isoglycyrrhizinate plus other liver protectants and those treated with other liver protectants. Patients treated with magnesium isoglycyrrhizinate plus other liver protectants had significantly lower median ALT levels on POD 7 and upon discharge from hospital, with a significantly reduction from postoperative baseline upon discharge from hospital in ALT levels compared to those without magnesium isoglycyrrhizinate treatment (Figure 4A and B). Moreover, patients treated with magnesium isoglycyrrhizinate plus other liver protectants had significantly higher rates of ≥ 50% reduction in the serum levels of ALT than those treated with other liver protectants on POD 3 and 7, and upon discharge from hospital (Figure 4C). Significantly more patients treated with magnesium isoglycyrrhizinate plus other liver protectants had normalized serum ALT levels on POD 7 (21.8% vs 11.8%, P = 0.015) (Figure 4D).
Meanwhile, patients treated with magnesium isoglycyrrhizinate plus other liver protectants also had significantly lower median AST levels on POD 7 and upon discharge from hospital, with a significantly reduction from postoperative baseline upon discharge from hospital in AST levels compared to those without magnesium isoglycyrrhizinate treatment (Figure 4E and F). Furthermore, significantly more patients treated with magnesium isoglycyrrhizinate plus other liver protectants had significantly higher rates of ≥ 50% reduction in the serum levels of AST on POD 7 (79.1% vs 75.2%, P = 0.029), and had normalized serum AST levels on POD 7 (63.6% vs 52.4%, P = 0.022) and upon discharge from hospital (70.0% vs 62.7%, P = 0.018) than those treated with other liver protectants (Figure 4G and H).
In this real-world, retrospective analysis of 1711 patients who underwent hepatectomy at tertiary care centers across China, perioperative magnesium isoglycyrrhizinate notably lowered the rate of postoperative hepatic injury in patients scheduled for hepatectomy. In addition, prophylaxis with magnesium isoglycyrrhizinate significantly attenuated the rise in ALT/AST levels and accelerated recovery of liver function post hepatectomy compared to lack of prophylaxis. Furthermore, even in the absence of prophylaxis, postoperative treatment with magnesium isoglycyrrhizinate was associated with significantly lower ALT/AST levels and higher rates of liver function recovery compared with those treated with other liver protectants only, suggesting that magnesium isoglycyrrhizinate should be incorporated into the treatment protocol for post hepatectomy injury. The findings indicate that perioperative magnesium isoglycyrrhizinate could be an effective management strategy for preventing and reducing the occurrences of perioperative liver injury in patients undergoing hepatectomy and as a postoperative treatment for hepatectomy-associated liver injury.
Perioperative liver injury is a serious complication of hepatectomy, and preventative strategies include ischemic preconditioning with intermittent Pringle maneuver and pharmacotherapy[30-32]. Magnesium isoglycyrrhizinate has been shown to exert hepatoprotective activities through a myriad of mechanisms including alleviation of oxidative stress, inhibition of autophagy, suppression of inflammatory response, and amelioration of ischemic injury[13,15,23]. Mag
Among patients with postoperative liver dysfunction, treatment with magnesium isoglycyrrhizinate, when compared with other liver protectants, significantly attenuated the rise of ALT and AST in patients who had undergone hepatectomy. This is similar to the studies by Mao et al[29] and Lv et al[34] showing that magnesium isoglycyrrhizinate notably abated the increase of ALT in patients with chronic liver disease and AST in patients with allogeneic hema
Strengths of this study include the large sample size and an overall representative patient population. In addition, the real-world study employed very broad inclusion criteria and accommodated hospital-specific differences and addressed confounders by matching patients who received prophylaxis and/or were treated with magnesium isoglycyrrhizinate and those who did not for four key clinical variables. Nevertheless, the study has several limitations. In this real-world study, limited treatment data were available such as comorbidities and concurrent medications. In addition, preoperative diagnosis and intraoperative variables such as estimated blood loss, blockade time, transfusion and operative time were not included in our real-world analysis. To mitigate confounding, we applied PSM to balance key baseline characteristics including sex, age, preoperative ALT level, and extent of liver resection between treatment groups. Nonetheless, the possibility of residual confounding from unmeasured variables cannot be excluded. Future studies incorporating these variables are needed to fully assess the efficacy of perioperative prophylaxis with magnesium isoglycyrrhizinate. We also had no control over the experience of hepatobiliary surgeons and their adherence to recommended surgical guidelines and good clinical practice. However, by accommodating hospital-specific differences and controlling key variables, the findings of the study could be applicable to different tertiary care hospitals. In addition, in the present cohort, alkaline phosphatase (ALP) levels were missing in a high proportion of patients, which may have influenced the interpretation of ALP assessment. Magnesium isoglycyrrhizinate, as a fourth-generation glycyrrhizin preparation in which β-glycyrrhizin is removed, and the α-isomer is purified to yield a 99.9% pure trans-isomer glycyrrhizinate, has been widely used for hepatic protection in China with a favorable safety profile. The findings from our study that consisted exclusively of Chinese patients are expected to facilitate studies of magnesium isoglycyrrhizinate among patient populations of other ethnicities.
This study provides real-world evidence that perioperative magnesium isoglycyrrhizinate is effective in attenuating the rise of aminotransferases post hepatectomy and accelerating postoperative liver function recovery, conferring hepatoprotection for more patients.
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