Clinical efficacy of glutathione combined with hepatosupplementation in the treatment of chronic hepatitis B

 Chronic hepatitis B is a chronic liver disease caused by infection with the hepatitis B virus (HBV), which is transmitted through blood, sex and mother-to-child. It is transmitted through blood, sex, and mother-to-child transmission. HBV can remain in the body for long periods, leading to liver inflammation and damage, and eventually to chronic hepatitis B. Symptoms of chronic hepatitis B usually appear months to years after infection. Some patients have symptoms that may appear months to years after infection. 

Symptoms of chronic hepatitis B usually appear months to years after infection, and some people may have no symptoms at all. Common symptoms include fatigue, loss of appetite, discomfort in the liver area, nausea and malaise [1]. In patients with chronic hepatitis B, jaundice, hepatomegaly and ascites may also occur. Antiviral therapy is the mainstay of treatment for chronic hepatitis B. The presence and replication of the hepatitis B virus in the body is the cause of the persistence of chronic hepatitis B. Antiviral drugs are currently used to suppress the hepatitis B virus. Currently, antiviral drugs are used to inhibit the proliferation of hepatitis B virus and reduce liver damage.

 

However, some patients are unable to completely clear the hepatitis B virus after long-term antiviral treatment, and long-term use of medication can lead to side effects and drug resistance, as well as immune disorders in some patients. This makes patients susceptible to other infections and inconsistent responses to treatment. One of the challenges is to regulate the patient's immune system to improve treatment effectiveness and prevent complications. Most patients have a long history of the disease, and the effects of prolonged viral infection can lead to impaired liver function and, in severe cases, to cirrhosis and liver cancer. In addition to controlling viral replication, clinical treatment needs to protect and repair the liver function of patients. However, the liver's self-repair ability is limited, and how to promote the recovery and repair of liver function remains a challenge [2]. Therefore, this article selects relevant patient cases from our hospital to comprehensively analyze the combination of viral therapy and liver function protection in patients with chronic hepatitis B, to improve the comprehensive therapeutic effect of the patients, which is now reported as follows.

 

1 Information and methodology

1.1 General information

One hundred and twenty patients with chronic hepatitis B from January 2022 to January 2023 were selected for the study, and were divided into a control group and an observation group according to the method of randomized numerical tables, with 60 cases in each group. In the observation group, there were 29 males and 31 females, aged 25-79 years, with a mean of 43.54±3.42 years. In the control group, there were 28 males and 32 females, aged 25-77 years, with an average of 42.95±3.98 years. Comparison of the general data between the two groups showed no statistically significant difference (P>0.05), and are comparable.

Inclusion criteria: age <80 years; signed informed consent.

Exclusion criteria: patients with hepatitis A or C; patients with malignant tumors; patients with cardiac diseases; patients with renal diseases.

 

1.2 Methodology

The control group was treated with Shujianning oral solution, the dosage was 20mL, to which was added 250mL of glucose injection solution with 5% concentration, for 4 weeks.

The observation group was treated with glutathione on this basis. Intravenous drip method, choose glutathione injection 40mL, add 5% concentration of dextrose injection 250mL, once a day, continuous treatment for 4 weeks.

 

1.3 Observation indicators

Observe the liver function of the two groups after 4 weeks of treatment, and select TBIL, ALT and AST as the indicators of liver function. Compare the treatment efficiency of the two groups. Observe the occurrence of adverse reactions in the two groups.

 

2 Results

2.1 Comparison of treatment recovery between the two groups of patients

The recovery of patients in the observation group was significantly better than that of patients in the control group, with a significant difference between the two groups (P<0.05). See Table 1 for details.

 

2.2 Comparison of treatment efficiency between the two groups of patients

The effective rate of treatment of patients in the observation group was significantly better than that of patients in the control group, and there was a significant difference between the two groups (P<0.05). For details, see Table 2.

 

2.3 Comparison of adverse reactions between the two groups of patients

Anxiety and depression in the observation group were significantly better than those in the control group, with significant differences between the two groups (P<0.05). For details, see Table 3.

 

3 Discussion

Chronic hepatitis B, which is caused by hepatitis B virus infection, can be characterized by a wide range of symptoms, and clinical management is challenged by the presence and replication of the virus, immune dysregulation, and the protection and repair of liver function. Further research and development of more effective therapeutic strategies are needed to better manage this disease. According to TCM, the etiology of chronic hepatitis B is mainly related to the attack of hepatitis B virus. According to TCM theory, hepatitis B virus is a dampness-heat toxicity that, when introduced into the body, causes internalization of dampness-heat toxicity, leading to liver dysfunction. The symptoms are categorized as liver depression, spleen deficiency, dampness, and blood stasis [3]. Liver depression refers to the stagnation of liver qi, which often manifests as irritability, chest tightness, and distension and pain in the chest and ribs; spleen deficiency refers to the weakness of spleen qi, which often manifests as loss of appetite and diarrhea; dampness refers to the retention of dampness and qi in the body, which often triggers symptoms of distension in the epigastrium and abdomen, nausea, and vomiting; and blood stasis refers to the obstruction of stasis of blood and blood, which often manifests as dysfunction of the internal organs and symptoms of hepatic sclerosis. According to TCM, the pathogenesis of chronic hepatitis B mainly includes liver qi stagnation, internalized dampness and heat, spleen and stomach dysfunction, and stagnation of qi and blood. Liver qi stagnation is the most common pathomechanism of chronic hepatitis B. It leads to liver qi dysfunction, which triggers spleen and stomach dysfunction, resulting in pathological changes such as internalized dampness and heat, and qi and blood stasis.

 

Heparin Injection is a kind of Chinese medicine preparation mainly used for the treatment of hepatitis. Its main ingredients include Inoceramus, Gardenia jasminoides, Scutellaria baicalensis, Ganoderma lucidum, Panax quinquefolium and other active ingredients. Yin Chen is a kind of herb with the function of detoxification, which can clear away heat and toxins, dredge the liver and benefit the gallbladder. It can increase the detoxification function of the liver, reduce the burden of the liver, and promote the regeneration and repair of liver cells, thus playing a role in the treatment of hepatitis. Gardenia glycoside has the function of clearing away heat and removing toxins, inducing choleretic and laxative. It can promote the secretion and excretion of bile, improve the function of biliary tract, reduce the inflammation of liver, and promote the recovery and repair of liver cells. Scutellaria baicalensis has anti-inflammatory, detoxifying and heat-clearing effects. It can reduce liver inflammation, inhibit viral replication and improve liver function. Ganoderma lucidum has antioxidant, antiviral and immunity-enhancing effects. It can reduce liver inflammation, enhance the antiviral ability of the liver and promote the repair and regeneration of liver cells. Banlangen has the function of clearing heat and detoxification and anti-virus, which can reduce liver inflammation, inhibit viral replication, and promote the recovery and repair of liver cells. Based on the efficacy of Liver Shuning Injection, it is mainly manifested in clearing heat and removing toxins, dredging the liver and inducing gallbladder, anti-virus and enhancing immunity. Through these effects, it can reduce liver inflammation, promote liver cell repair and regeneration, improve liver function, and thus achieve the purpose of hepatitis treatment.

 

Reduced glutathione is widely found in human cells, especially in liver cells, which are the richest in reduced glutathione. This substance not only participates in the body's trihydroxy acid cycle, but also plays a significant role in glycogen conversion, fat accumulation, and protein metabolism, and activates a variety of enzymes, which promotes metabolism and plays a significant role in the normal functioning of liver cells. Reduced glutathione has a significant effect on the normal functioning of liver cells. Reduced glutathione plays an important role in the protection of liver cells, as it is an important participant in the antioxidant cycle by combating lipid peroxidation [4].

 

Chronic hepatitis B is a long term chronic viral hepatitis with changes in TBIL (total bilirubin), ALT (alanine aminotransferase) and AST (aspartate aminotransferase). In patients with chronic hepatitis B, TBIL is usually elevated as liver function deteriorates. Hepatitis B virus infection causes damage to liver cells and the liver is unable to metabolize bilirubin properly, allowing it to accumulate in the blood. Elevated TBIL may therefore be an indicator of chronic hepatitis B. Clinicians usually measure TBIL in the blood by testing the blood for bilirubin. Clinicians usually measure TBIL in the blood to assess the liver function of patients. In the observation group, after treatment with glutathione and Heparin injection, the TBIL level decreased by more than 80%, which is a significant advantage compared with the control group. ALT and AST are also commonly used indicators of liver function, compared with TBIL, ALT and AST mainly exist in liver cells, and when liver cells are damaged, the damaged stem cells will release ALT and AST into the blood through the blood circulation, leading to an increase in ALT and AST. In patients with chronic hepatitis B, elevated ALT and AST are usually associated with active viral replication, hepatocyte damage, and inflammation. Hepatitis B virus can infect liver cells and cause an inflammatory response, which can lead to liver injury and hepatocyte damage, resulting in elevated ALT and AST. From the patient data obtained in this controlled trial study, it can be seen that before the treatment, the ALT and AST levels of the two groups of patients were elevated to 80 mmoL, which is more than 70% of the elevated level compared to the patients in the physical examination; after four cycles of treatment, the overall ALT and AST levels of the patients decreased to a good extent, especially in the observation group, where the ALT and AST levels decreased by more than 90%, compared to the control group. In particular, the patients in the observation group showed a decrease of more than 90% in ALT and AST levels, which was significantly different from the patients in the control group.

 

The occurrence of chronic hepatitis B is closely related to the obstruction of hepatic microcirculation. After infection with hepatitis B virus, the hepatic microcirculation is damaged, and bilirubin is obviously elevated, which brings about the obstruction of microcirculation and further deepens the stagnation of blood flow in patients [5]. The application of Liver Shuning Injection can help to relieve the stagnation of blood flow, slow down the damage of capillaries and accelerate the excretion function of capillaries, so that bilirubin can be effectively discharged from the biliary tract, thus further improving the effectiveness of patient treatment. From the total effectiveness of treatment in the Observation Group, it can be seen that after the use of Liver Shuning Injection, the patients' bilirubin levels dropped by 70% on average, and the total bilirubin levels of patients in the Control Group who used only Liver Shuning Injection decreased by 70% on average. In the control group, the total bilirubin level of patients who used Liver Shunning Injection alone also decreased by more than 65% on average, which indicates that the application of Liver Shunning Injection has a significant effect on alleviating the microcirculation obstacles of patients.

 

The main ingredients in Liver Shuning Injection are: Panax quinquefolium, Yin Chen, Scutellaria baicalensis, Ganoderma lucidum and Gardenia jasminoides which can effectively enhance the circulation of liver blood cells and effectively improve the circulation level of patients, and at the same time, it has the ability to promote two-way regulation of the body, enhance the immunity of the body, and further improve the tolerance ability of the liver cells to ischemia and ischemia, so as to reduce the destruction of hepatitis B virus on patients' liver cells and further control inflammatory cell infiltration and enhance the internal regeneration of patients' liver cells. Control inflammatory cell infiltration and enhance the regeneration of liver cells in patients. Currently, the treatment of patients with chronic viral hepatitis B is mainly based on hospitalization and absolute bed rest, with adequate nutritional support. Glutathione intake ensures nutritional support, supports quality improvement, and ensures a high caloric and protein intake.

 

Abstaining from smoking and alcohol, for some severely infected patients, it may be necessary to reduce the protein in the diet as much as possible, under this circumstance, guaranteeing sufficient intake of glutathione can also help to improve the metabolic level of the liver cells of the patients, promote the recovery of liver function of the patients and reduce the damage caused by viral hepatitis B to the liver function of the patients, and at the same time, there is a good combination of glutathione and hepatic shuning injection, and the combination of the two can maintain the balance of water and electrolyte function in the liver cells of patients, and further improve the liver function of patients. At the same time, glutathione and heparin injection have a good combination effect, and the combination of these two treatments for patients with viral hepatitis B can maintain the balance of water and electrolyte function in the liver cells of patients, and further improve the function of the liver of patients.

 

Gan Shuning Injection is mainly based on the composition of "Yin Chen Artemisia Tang" in the "Treatise on Typhoid Miscellaneous Diseases", which contains active ingredients that can have synergistic effects on each other. In particular, Scutellaria baicalensis, Artemisia capillaris, Ganoderma lucidum and Radix et Rhizoma Cymbopogonis can cool the blood, benefit the pharynx, clear away heat and detoxify the toxin, and have a significant inhibitory effect on the replication, transcription, and transmission of the hepatitis B virus; together with the adequate intake of glutathione, it can further enhance the immune function of the patient, and has the effect of clearing away and relieving fever; the use of Radix et Rhizoma Cymbopogonis can help reduce the jaundice and have a good protective effect on the secretion of the digestive juices and bile. The use of Yin Chen can reduce jaundice and protect the secretion of digestive fluid and bile. Combined with glutathione, it can further protect the liver cells of patients, and to a certain extent promote the regulation of myocardial function of patients, so that the serum aminotransferase and blood lipids of patients can be significantly reduced, further reducing the immune response of liver cells of patients under the attack of viral hepatitis B, so that the immune activity of patients is significantly enhanced. Under the intervention of the combination of drugs, the overall anti-inflammatory and decongestive effects of the patients in the observation group and the level of hepatocyte protection and hepatocyte nutrition have been effectively improved, so that the level of the relevant liver function indexes of the patients has been reduced to a level higher than that of the control group.

 

According to Qi Jinghu[1] , TBIL, ALT and AST indexes in patients with chronic hepatitis B will show certain changes, mainly including the increase of TBIL, and the increase of ALT and AST. Changes in these markers can be used as indicators of liver function and severity of the disease, which can help clinicians make diagnostic and therapeutic decisions. Xu Yongping[2] concluded that the changes in TBIL, ALT and AST may vary between patients, and that the specific situation needs to be evaluated and analyzed on an individual basis. From the actual situation of the observation group in this paper, under the intervention of the combination of drugs, the decrease of liver function indexes of the patients in the observation group was more than 60%, and the effective rate of treatment was increased by 20%, and the safety of treatment was not significantly affected. This is consistent with the results of literature research.

 

CRP is highly sensitive to inflammation and is an important indicator for evaluating the degree of inflammatory response. In this study, the levels of CRP, IL-6 and TNF-α in the observation group were lower than those in the control group in the 3d postoperative period (P<0.05). This suggests that low-position small incision surgery is less traumatic to the body, and the degree of postoperative inflammatory reaction is less severe, which contributes to the rapid recovery of tissue damage [6]. The FT3, FT4, TT3 and TT4 of the two groups were comparable at 7d postoperatively (P>0.05). It is confirmed that this procedure does not significantly affect the normal thyroid function, and the patients' thyroid function recovers faster after the operation.

In conclusion, the low small incision treatment of benign thyroid nodules is more effective, less traumatic, with less postoperative inflammation, fewer complications, and less impact on thyroid function, and is worth popularizing.

 

References:

[1] YANG Guofeng, YU Xuexue. Observation on clinical effect of low small incision thyroid surgery for benign thyroid nodules[J]. Henan Medical Research,2017,26(7):1295-1296.

[2] Zong Hongfei. Comparative analysis of low small incision and traditional thyroid surgery for benign thyroid nodules[J]. Zhongguo Nankang Medicine,2017,29(18):40-41.

[3] JI Lansheng, YU Dongmei, HAO Jianhua. Therapeutic effects of low-level small incision and traditional thyroid surgery on benign thyroid nodules[J]. China Medical Abstracts Otolaryngology,2022,37(5):13-15.

[4] Su Zhenxi, Xu Xing, Cao Feng, et al. Exploration of the efficacy of low-level small-incision thyroid surgery for benign thyroid nodules[J]. Chinese Drugs and Clinics, 2021,21(11):1845-1848.

[5] XU Zhao-Wei, ZANG Jian-Feng. Comparison of clinical effects between low small incision and traditional thyroid surgery for benign thyroid nodules[J]. Modern Diagnosis and Treatment,2020,31(19):3137-3139.

[6] WEI Ning, XU Changhao, GAO Chengqiu. Observations on the clinical effects of traditional thyroid surgery and low-level small incision surgery for benign thyroid nodules[J]. China Medical Abstracts Otolaryngology,2022,37(4): 93-94,90.

 

Is glutathione reductase useful in hepatitis B virus-infected patients?

 Hepatitis B virus (HBV) infection There are about 257 million chronic HBV-infected people in the world[1] . In China, there are about 70 million cases of chronic HBV infection, of which about 20-30 million cases of Chronic Hepatitis B (CHB)[2] .

 

Current studies have shown that the imbalance between oxidative and antioxidative damage in CHB patients plays an important role in the progression of viral hepatitis to hepatocellular carcinoma [3]. Glutathione reductase (GR) is one of the most important enzymes in the redox system of the human body, and it is the main flavoprotein enzyme that maintains the level of reduced glutathione in cells. GR converts oxidized glutathione to reduced glutathione with the participation of NADPH. Reduced glutathione plays an important role in preventing the oxidative decomposition of hemoglobin, maintaining the activity of mercapto proteins, and ensuring the reducibility of mercapto proteins and cellular integrity [4].

 

In recent years, the significance of GR in patients with CHB has been gradually emphasized, and it has been regarded as one of the important complementary indicators for liver function tests. However, the trend of GR in viral hepatitis or in animal models of liver injury is controversial [5-8]. In this study, we investigated the differences in the distribution of serum GR activity between apparently healthy populations and HBV-infected diseases, as well as the correlation and differences with traditional liver function indices, in order to provide a basis for the clinical application of GR in the assessment of HBV-infected liver injury.

 

1 Information and methodology

1.1 General information Retrospective analysis From August 2019 to December 2019, 139 patients with liver diseases (112 patients with CHB, 12 patients with cirrhosis, and 15 patients with hepatocellular carcinoma), including 95 males and 44 females, with an age range of 19-76 years old, were seen in the Gastroenterology and Infection Departments of the Second People's Hospital of Jianli City, Hubei Province, because of HBV infection. In addition, 56 cases of apparent health checkups were selected from our medical checkup center, of which 30 cases were male and 26 cases were female, with an age range of 20-60 years old.

 

Inclusion criteria for healthy people: (1) age ≥ 18 years; (2) all HBV serological markers negative or only HBsAb positive, hepatitis C virus serum antibody negative; (3) traditional liver function tests within the normal range: aspartate aminotransferase (AST) ≤ 40 U/L for men and ≤ 32 U/L for women; alanine transaminase (ALT) ≤ 41 U/L for men and ≤ 33 U/L for women; total bilirubin (TBIL) ≤ 26 mmol/L for men and ≤ 21 mmol/L for women; direct bilirubin (DBIL) ≤ 8 mmol/L; and direct bilirubin (DBIL) ≤ 8 mmol/L for women. Total bilirubin (TBIL) ≤26 mmol/L for men and ≤21 mmol/L for women; direct bilirubin (DBIL) ≤8 mmol/L; alkaline phosphatase (ALP) 10-71 U/L for men and 6-42 U/L for women; and gamma-glutamyltranspeptidase (γ-GT) 10-71 U/L for men and 6-42 U/L for women. Exclusion criteria for healthy people: people with major organic lesions, history of tumors, history of liver transplantation, oral drug users, patients with HBV-infected liver diseases Inclusion criteria: (1) Age ≥ 18 years; (2) HBsAg-positive surface antigen of hepatitis B virus, negative serum antibody to hepatitis C virus. （Exclusion criteria for HBV-infected liver disease were: liver failure, combination of diseases other than liver, and history of liver transplantation.

 

1.2 Instruments and reagents   

GR kit (Jiangxi Lecheng Biological Co., Ltd., UV enzyme assay), reference range 33-73 U/L, detected by Beckman AU5800 automatic biochemical analyzer. AST, ALT, TBIL, DBIL, ALP, γ-GT were detected by Beckman original kit. Hepatitis B virus 5 and anti-hepatitis C virus antibody were detected by Abbott Automatic Immunoassay Analyzer Architect i200sr and its original reagents, and HBV-DNA was detected by AGS8830 real-time fluorescence quantitative PCR instrument produced by Hangzhou AnYu Technology Co.

 

1.3 Methodology   

Three tubes of 4-6 mL of venous blood from each enrollee were centrifuged at 1912×g for 10 min to separate the serum. If it was too late for testing within 3 hours, the serum was frozen at -80 ℃ until testing. General clinical data were collected.

 

1.4 Statistical processing  

Statistics were performed using SPSS 16.0 software, and data were tested for normality using the Kol-mogorov-Smirnov test. Skewed measures were expressed as median (interquartile spacing), and comparisons between the two groups were made using the Mann-Whitney U test. Correlations were analyzed by Spearman's rank correlation, and a difference of P<0.05 was considered statistically significant.

 

2 Results

2.1 Comparison of liver function test results between hepatitis B virus-infected liver disease groups and the control group The liver function test indexes and age of the analyzed population were tested for normality, and only the age showed a normal distribution (age, P=0.163), and all the liver function indexes (GR, ALT, AST, ALP, GGT, TBil, DBIL) showed a skewed distribution, and all the data were expressed as the median (interquartile spacing), and the analysis method was non-parametric test. Therefore, all data were expressed as median (interquartile spacing) and analyzed by nonparametric test.

 

For the healthy subjects and the disease groups in this experiment, there was a significant difference in age composition (P<0.05). For traditional biochemical indicators, AST, ALT and γ -GT increased with the progression of liver disease after hepatitis B virus infection, and were significantly higher in the hepatocellular carcinoma group than in the cirrhosis group, and in the cirrhosis group than in the chronic hepatitis B group; they were significantly higher in the chronic hepatitis B group than in healthy subjects; TBIL, DBIL and ALP were significantly higher in the disease group than in healthy controls, and were significantly higher in the cirrhosis group than in the chronic hepatitis B group; but there was no significant difference between the chronic hepatitis B and cirrhosis groups; GR was significantly different in the chronic hepatitis group than in the healthy subjects. TBIL, DBIL and ALP were significantly higher in the disease group than in healthy controls, cirrhosis group and hepatocellular carcinoma group respectively, but there was no significant difference between the cirrhosis and hepatocellular carcinoma groups; GR was significantly higher in the chronic hepatitis group than in healthy controls at 59.4 (54.7-67.3) U/L (P < 0.001), and in the cirrhosis group at 73.1 (57.3-96.7) U/L (P < 0.001), while in the chronic hepatitis group, it was higher than that in the chronic hepatitis group (P < 0.001). In the cirrhosis group, 73.1 (57.3-96.7) U/L was significantly higher than that in the chronic hepatitis group (P<0.001), but in the hepatocellular carcinoma group, the concentration of GR was significantly lower than that in the other three groups (P<0.001), 26.5 (14.2-47.9) U/L (P<0.001). See Table 1.

 

2.2 Comparison of GR in various subgroups of chronic viral hepatitis B

Due to the small number of samples in the cirrhosis and hepatocellular carcinoma groups and the fact that the pattern of change of GR is different from other indexes, only the CHB group was further analyzed. The CHB patients were divided into different subgroups according to different criteria.

In patients with CHB, GR was significantly higher than in healthy controls when all other liver function tests were normal, and GR exceeded the upper limit of the reference interval in 6 cases, with a positivity rate of 8.2% (6/73). However, there was no significant change in GR in the group with any positive liver function tests compared to the group with normal liver function tests.

When patients with CHB were grouped according to whether they were HBeAg positive or negative, all indicators except TBIL were significantly higher in these two subgroups than in healthy controls, respectively. However, only ALP was higher in the HBeAg-positive CHB subgroup than in the HBeAg-negative subgroup.

The patients with CHB were categorized according to HBV-DNA positive or negative, and all the indexes were significantly higher in the DNA-positive group than in the healthy control group, while in the DNA-negative group, only GR, AST, and ALP were significantly higher than in the healthy control group, and GR was significantly higher in the DNA-positive group than in the DNA-negative group. See Table 2.

 

2.3 Correlation between GR and other indicators in chronic viral hepatitis B

Spearman's correlation analysis showed that in patients with CHB, GR was significantly and positively correlated with other indices of conventional liver function (ALT, AST, TBIL, ALP, GGT) and DNA content (after conversion from DBIL), with the exception of DBIL.  In patients with CHB, except for DBIL, GR showed a significant positive correlation with other indicators of conventional liver function (ALT, AST, TBIL, ALP, GGT) and DNA content (after lg conversion). See Table 3

 

3 Discussion

Hepatocyte mitochondria, hepatic blast cells and inflammatory cells all produce reactive oxygen species (ROS) and free radicals, and the liver also exerts antioxidant effects through protein synthesis. In the pathogenesis of hepatitis B, there is a broad spectrum of oxidative stress that occurs at all levels, including lipids, DNA and proteins[3] . Glutathione peroxidase (GPX) and GR are important components of the glutathione (GSH) antioxidant system, which can scavenge ROS and repair oxidative damage[4] . In this study, GR was elevated in viral hepatitis B before conventional liver enzymes and bilirubin, and was further elevated in patients with cirrhosis of viral hepatitis B and decreased in hepatocellular carcinoma of hepatitis B virus infection. In the available literature, the pattern of changes in GR in hepatitis B virus-infected liver injury varies. Li Shuli et al. showed that GR levels were elevated in patients with chronic hepatitis B virus[7] , and Fan Yuchen et al. showed that GR was decreased in patients with CHB[8] .

 

In patients with CHB, the results of this study were consistent with those of Li Shuli et al [7]. Through the statistics of traditional liver function tests, it can be concluded that the patients with CHB enrolled in this study were in the state of mild liver insufficiency, and the liver function indicators such as aminotransferases were much lower than those in the study by Fan Yuchen et al[8] . A possible mechanism is that the liver maintains the balance of ROS and antioxidants in the body under normal conditions. When HBV virus infects the human body, oxidative stress is triggered by proteins such as HBx protein, HBsAg and HBcAg [9-11], and the body recycles oxidized glutathione by increasing GR levels to improve the harmful environment in the body [12]. Therefore, the elevation of GR precedes the conventional changes in liver enzyme profile and bilirubin. However, when the liver is subjected to successive oxidative damage, ROS damage is further increased, leading to inflammation and fibrosis, regenerative nodules and loss of liver function[13- 14] . Moreover, when liver injury is further increased, too much ROS are produced and the compensatory increase in GR is less than the amount consumed, leading to a decrease in GR. In patients with hepatocellular carcinoma, the GSH microcirculatory system may be disrupted in cancer cells, resulting in a compensatory increase in GR. However, the number of hepatocellular carcinoma patients in this study was small, and further expansion of the sample size is needed to verify this conclusion.

In this study, GR was not associated with the negativity or positivity of HBeAg, but with the negativity or positivity of HBV-DNA. Further analysis showed a positive correlation between GR and HBV-DNA (r=0.396, P<0.001), suggesting that the oxidative damage increased further with the increase of viral load[15] . This finding is consistent with the study of Tianlu Zhou et al [16].The relationship between GR and HBV-DNA suggests that GR may be used as one of the indicators for antiviral monitoring of hepatitis B virus.

 

There are some limitations to this study: (1) The statistical results of this study showed a positive correlation between GR and age. The control group in this study was not matched by age and gender. (2) The number of cases of cirrhosis and hepatocellular carcinoma in this study is relatively small, which needs to be verified by enlarging the sample size.

 

4 Conclusion

GR is elevated in patients with hepatitis B virus infection in the early stages of liver injury and can be used as an important supplement to traditional liver function tests and as a monitor of the effectiveness of antiviral therapy for hepatitis B virus.

 

References:

[1]Ran Xu Zhu,Wai-Kay Seto,Ching-Lung Lai, et al. Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region[J]. Gut Liver, 2016,10(3):332-339.

[2]Liu J, Liang W, Jing W, et al. Count down to 2030:eliminating hepatitis B disease,China[J]. Bull World Health Organ, 2019,97(3): 230-238.

[3]Alavian SM, Showraki A. Hepatitis B and its Relationship With Oxidative Stress[J]. Hepat Mon, 2016,16(9):e37973

[4] Saeed Samarghandian, Mohsen Azimi -Nezhad, Tahereh Farkhon- deh, et al. Anti-oxidative effects of curcumin on immobilization - induced oxidative stress in rat brain, liver and kidney [J]. Biomed Pharmacother,2017,87:223-229.

[5] Bhasha Shanmugam,Kondeti Ramudu Shanmugam,Sahukari Ravi, et al. Exploratory Studies of (-)Epicatechin, a Bioactive Compound of Phyllanthus niruri, on the Antioxidant Enzymes and Oxidative Stress Markers in Dgalactosamine induced Hepatitis in Rats: a Study with Reference to Clinical Prospective[J]. Pharmacogn Mag, 2017,13(Suppl 1):56-62.

[6] Kumata H, Wakui k, Suzuki H, et al. Glutathione reductase activity in serum and liver tissue of human and rat with hepatic damage[J]. Tohoku J Exp Med, 1975, 116(2):127-132.

[7] LI Shuli, LU Shanzhi, WANG Jun, et al. Clinical value of serum glutathione reductase activity in patients with hepatitis B liver injury[J]. International Journal of Laboratory Medicine , 2020, 41(15):1844-1848.

[8] FAN Yu-Chen, WANG Kai, HAN Liyan, et al. Effects of interferon α-2b on oxidative damage in patients with chronic hepatitis B[J]. Chinese Journal of Experimental and Clinical Virology ,2007,21(1):23 - 25.

[9] Ji-Hua Ren, Xiang Chen, Li Zhou, et al. Protective Role of Sirtuin3 (SIRT3) in Oxidative Stress Mediated by Hepatitis B Virus X Pro- tein Expression[J]. . PLoS One,2016,11(3): e0150961...

[10] Hong Kim, Seoung-Ae Lee, You-Sub Won, et al. Occult infection related hepatitis B surface antigen variants showing lowered secre- tion capacity[J]. . World J Gastroenterol, 2015, 21(6):1794-1803.

[11] HyunJoo Lee, Hong Kim, Seoung -Ae Lee, et al. Upregulation of endoplasmic reticulum stress and reactive oxygen species by natu- rally occurring mutations in hepatitis B virus core antigen[J]. J Gen Virol,2015,96(Pt 7):1850-1854.

[12] Alexander V Ivanov, Vladimir T Valuev-Elliston, Daria A Tyuri- na, et al. Oxidative stress, a trigger of hepatitis C and B virus-in- duced liver carcinogenesis[J]. Oncotarget,2017, 8(3):3895-3932.

[13]Mihnea Marian Pomacu,Maria Diana Trasca,Vlad Padureanu, et al. Interrelation of inflammation and oxidative stress in liver cir- rhosis[J]. Exp Ther Med,2021,21(6):602.

[14] Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxi- dants in normal physiological functions and human disease[J]. Int J Biochem Cell Biol, 2007,39(1):44-84.

[15] Bolukbas C, Bolukbas FF, Horoz M, et al. Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection [J].  BMC Infectious Diseases 2005,5:95.

[16]T Zhou,A A Evans,W T London, et al. Glutathione S-transferase expression in hepatitis B virus -associated human hepatocellular carcinogenesis[J]. . Cancer Res,1997,57(13):2749-2753.

 

Does glutathione reductase have an impact on the prognostic assessment of patients with gastric cancer?

 Gastric cancer (GC) is a malignant tumor of the gastric mucosal epithelium with a high incidence and low cure rate, and is one of the most common malignant tumors in the world, with adenocarcinoma accounting for 95% of the tissue types[1] . According to the latest statistics, gastric cancer accounts for 770,000 deaths and 1.09 million cases of gastric cancer diagnosed each year worldwide [2]. Helicobacter pylori is a tumorigenic factor of gastric cancer, and 40-60% of adults in China are infected with Helicobacter pylori, which is one of the reasons for the high incidence of gastric cancer in China [3]. There are no obvious clinical symptoms in the early stage of gastric cancer, and the diagnosis is often made at an advanced stage, and the 5-year survival rate of gastric cancer in China is less than 30% due to metastasis and drug resistance [4]. In China, the 5-year survival rate of gastric cancer is less than 30% due to cancer metastasis and drug resistance[4] . Traditional tumor markers, such as CEA, CA199, etc., are not suitable for the diagnosis of early gastric cancer due to the lack of specificity and sensitivity.

 

Glutathione reductase (GR) was first found in prokaryotes and eukaryotic cells of plants and animals, and in humans, it is mainly found in erythrocytes, monocytes, macrophages, and tissue cells of the heart, liver, and kidneys, and it is a monomeric riboflavin-type oxidoreductase [5], which is an important component of the human redox system. GR uses nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor to catalyze the formation of reduced glutathione (GSH) from oxidized glutathione (GSSG). This enzyme increases the ratio of GSH/GSSG and maintains a high level of GSH in the body, which is beneficial to the body's antioxidant activity[6] . At present, the clinical application of GR is mainly reported in hepatitis, cirrhosis and metastatic hepatocellular carcinoma [7-8], but the application of GR in gastric cancer patients has not been reported. In this study, 337 patients with gastric cancer were collected as the observation group and 135 healthy medical checkups were collected as the control group to compare the differences in serum GR activity concentration between the two groups, and to analyze the changes in serum GR activity concentration in patients with gastric cancer with different clinicopathological characteristics and the changes in GR activity concentration before and after surgery, with the aim of exploring the value of the application of GR in the assessment of prognosis of gastric cancer.

 

1 Information and methodology

1.1 General Information   

Ninety gastric cancer patients treated in Jiangxi Cancer Hospital from December 2018 to December 2019 and 247 gastric cancer patients treated in the Second Affiliated Hospital of Nanchang University from 2020 to 2021 were selected as the observation group, and 135 health checkups were selected as the control group.337 patients in the observation group included 212 males and 125 females, with a minimum age of 20 years old and a maximum age of 90 years old, and a mean age of (6136±11.08 years old). The minimum age of the patients was 20 years old, the maximum age was 90 years old, and the average age was 61.36±11.08 years old; the clinical stages were: 61 cases of Stage I (18.1%), 75 cases of Stage II (22.3%), 165 cases of Stage III (49.0%), and 36 cases of Stage IV (10.7%).There were 87 males in the control group, and the number of patients who had been treated in the control group was 137, and the number of patients who had undergone medical checkups was 135.

There were 48 female cases, with age ranging from 26 to 89 years old, and the average age was (48.00±14.32) years old. The correlation coefficient between age and GR activity was -0.26, with no statistically significant difference (P=0.639>0.05), and there was no statistically significant difference between gender and GR activity (P=0.383>0.05).

 

1.2 Testing equipment and reagents   

The GR testing equipment of Jiangxi Cancer Hospital was Hitachi 7600 (210) automatic biochemical analyzer, and the testing equipment of the Second Affiliated Hospital of Nanchang University was Canon TBA-FX8 automatic biochemical analyzer, and the reagents were provided by Jiangxi Lecheng Technology Co. All the reagents were provided by Jiangxi Lecheng Science and Technology Co.

 

1.3 Inclusion criteria   

Inclusion criteria of the observation group: (1) meeting the clinical diagnostic criteria of gastric cancer and diagnosed as gastric cancer; (2) normal liver and kidney functions;

(3) No other tumor disease except gastric cancer . Inclusion criteria for the control group: (1) people who came to the hospital for health checkups; (2) normal liver and kidney functions; (3) no tumors.

 

1.4 Methodology

1.4.1 Information collection   

Gastric cancer patients and health checkups treated in Jiangxi Provincial Cancer Hospital and the Second Affiliated Hospital of Nanchang University from December 2018 to December 2021 were retrospectively analyzed, and the observation and control groups were screened according to the inclusion criteria.

 

1.4.2 Analyzing the difference in GR activity between the observation and control groups   

Differences in GR activity were analyzed in 337 cases of gastric cancer in the observation group and 135 healthy controls.

1

.4.3 Analysis of different clinicopathological characteristics of the observation group

Differences in GR activity were analyzed in 337 cases of gastric cancer in the observation group with different age, gender and clinicopathological stages.

 

1.4.4 Statistical methods  

The collected data were statistically analyzed using SPSS 21.0 software. The P-P plot was used to test whether the data were normally distributed, and continuous variables were expressed as mean ± standard deviation (x ± s). Differences between the two groups were analyzed by independent samples t-test, differences between the observation group before and after surgery were analyzed by paired samples t-test, multiple comparisons were analyzed by one-way ANOVA, and correlation analyses were performed by Pearson's method, and differences were considered statistically significant if P<0.05.

 

2 Results

2.1 Comparison of serum GR activity between observation and control groups   

The P-P plot test showed that the GR activity data were normally distributed, as shown in Figure 1. Serum GR activity in the observation group (51.73±13.15)U/L, and in the control group (56.89±10.43)U/L, the difference was statistically significant (P=0.000<0.05), see Table 1.

 

2.2 Comparison of serum GR activity in patients with different clinicopathologic characteristics in the observation group  

It was found that there was no statistically significant difference between the serum GR activity and the age and gender of the patients (P>0.05), while there was a statistically significant difference between the serum GR activity and the clinical stage of the patients (P=0.000<0.05), as shown in Table 2.

 

2.3 Changes in GR activity before and after surgery and chemotherapy in the observation group   

The preoperative GR activity was higher than the postoperative GR activity in 74 patients with gastric cancer who underwent surgical treatment, and the difference was statistically significant (P<0.05). The difference was statistically significant (P<0.05).

 

3 Discussion

Gastric cancer is one of the most common malignant tumors in the digestive system. With the development of China's economy and the change of people's life style and dietary habits, the incidence rate and mortality rate of gastric cancer have been increasing year by year, and the trend of incidence of gastric cancer has been developing towards the younger age group [9]. The five-year survival rate of early gastric cancer is significantly higher than that of late gastric cancer, and early detection, diagnosis and treatment are of great significance in reducing the mortality rate and improving the prognosis of gastric cancer [10]. At present, the "gold standard" for the diagnosis of gastric cancer is gastroscopy and submucosal tissue biopsy, which is expensive, highly uncomfortable for patients in the process of detection, poorly accepted by patients, and unsuitable for large-scale clinical application. Tumor markers used to detect gastric cancer are mainly CEA, CA19-9 and CA72-4, but the sensitivity and specificity are not high in the general population, and they are mainly used for the detection of postoperative recurrence and metastasis [11].

 

GR is widely present in the human body and catalyzes the reduction of GSSG to GSH, which has the effect of enhancing the antioxidant, anti-inflammatory and antiproliferative properties of the body. The present study showed that the difference in serum GR activity concentration between gastric cancer patients and healthy subjects was statistically significant (P=0.000<0.05). Further analysis of serum GR activity concentration in gastric cancer patients with different clinicopathological characteristics showed that the difference in GR activity concentration between different ages and genders was not statistically significant (P>0.05), while the difference in GR activity concentration between different clinical stages was statistically significant (P<0.05), and the GR activity gradually increased with the progression of the disease, but the concentration of GR activity was significantly lower after the operation than that before the operation (P<0.05). However, the concentration of GR activity after surgery was significantly lower than that before surgery (P<0.05). These results suggested that serum GR activity concentration was not closely related to the development of gastric cancer. Oxygen free radicals can induce cell mutation, apoptosis, chromosomal aberrations and carcinogenesis[12] , and GR is an important component of the antioxidant system in the body.Yalcin Kekec et al.[13] showed that GR was significantly higher in gastric cancer tissues than in paracancerous tissues. In the present study, we analyzed the GR activity of 337 patients with gastric cancer in two tertiary hospitals, covering stages I, II, III, IV, preoperative and postoperative, and excluding the interference of liver function abnormalities and other tumors, so the analysis results have a good credibility. However, further basic research is needed to investigate the pathway through which GR promotes the development of gastric cancer.

 

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