LI Chu-yi, WANG Jun-ke, LI Bin, WEN Xue, WEI Xiao-jing, YU Xiao-hui?

1. Department of Gastroenterology, 940 Hospital of Joint Service of PLA, Gansu Lanzhou 730050,China

2. Ningxia Medical University, Ningxia Yinchuan 750004,China

Keywords:Artificial liver Chronic and acute liver failure Impact assessment

ABSTRACT Objective: To study and evaluate the clini1cal effect of plasma exchange in the adjuvant treatment of chronic and acute liver failure. Methods:Totally 60 patients with chronic and acute liver failure in our department were divided into two groups. The control group received comprehensive treatment and the plasma exchange group received plasma exchange. The changes of total bilirubin(TBIL) ,PT percentage activity(PTA), alanine aminotransferase(ALT), aspartate aminotransferase(AST), albumin(ALB), interleukin-6(IL-6), procalcitonin(PCT) and C-reactive protein (CRP) were measured after treatment, and were assessed in terms of the degree of relief of clinical symptoms. Results: TBIL, ALB, Alt, AST, IL-6, PCT and CRP in the two groups decreased and PTA increased compared with those before treatment, but the curative effect of the treatment group was better than that of the control group (P＜0.05).The total effective rate of the treatment group was 80.0%, which was higher than 46.6% of the treatment group (P＜0.05).Conclusion: Plasma exchange can help to improve the liver function, remove a large number of inflammatory factors, promote the recovery of liver function and improve the prognosis of patients with chronic and acute liver failure.

1. Introduction

Chronic acute liver failure has a rapid disease progression and a high mortality rate, which brings a serious burden to patients. Drugs are the basic treatment of the disease, but liver protection drugs are difficult to remove cytotoxic substances. The reason is that drugs have limited clearance of inflammatory mediators and bilirubin that aggravate liver function damage, and removing inflammatory mediators and reducing bilirubin are the key to improving liver function. Plasma exchange (PE) is one of the most widely used artificial liver technologies in clinic at present. It can not only remove various inflammatory mediators and toxic substances produced by metabolism in the body, but also supplement various nutrients required by the human body. In particular, it can significantly reduce hyperbilirubinemia and play an important auxiliary role in the treatment of acute liver failure [1].This study mainly collected 60 patients with chronic and acute liver failure for clinical study.

2. Materials and methods

2.1 General information

Sixty patients with chronic acute liver failure admitted to our department from August 2018 to July 2020 were divided into plasma exchange group and control group (30 cases each), aged 20-75 years. Among them, there were 17 males and 13 females in the control group, aged 23-75 years, with an average of (49.38±13.24)years. Etiological classification: 21 cases of HBV (hepatitis B virus), 3 cases of HCV (hepatitis C virus), 2 cases of alcoholic liver disease, and 4 cases of AIH (autoimmune hepatitis). In the plasma exchange group, there were 20 males and 10 females, aged from 14 to 73 years, with an average of (44.08±16.10) years. The etiological classification included 17 cases of HBV, 4 cases of HCV, 3 cases of alcoholic liver disease and 6 cases of AIH (autoimmune hepatitis).

2.1.1 Inclusion criteria

All patients met the diagnosis of chronic and acute liver failure in the guidelines for the diagnosis and treatment of liver failure (2018 version) [2]. Yellow staining of skin and sclera appeared rapidly, and serum TBIL≥10×ULN or daily rise≥17.1μ mol/L;With bleeding,PTA≤40% (or INR≥1.5) can be divided into 3 types according to different chronic liver diseases. Type A: chronic and acute liver failure on the basis of chronic non cirrhotic liver diseases; Type B:it occurs on the basis of compensated cirrhosis, usually within 4 weeks; Type C: occurs on the basis of decompensated cirrhosis.

2.1.2 Exclusion criteria

(1) Tumor disease, serious disease of blood system and lung,serious disease of cardiovascular and cerebrovascular diseases;(2)Patients with acute, subacute and chronic liver failure; (3) Allergic to the drugs and blood products used in this study; (4) Recent active bleeding or possible bleeding;(5) Pregnant or lactating women;(6)Persons with consciousness disorders and mental and psychological diseases.

2.1.3 Rejection criteria

Transfer to another hospital, automatic discharge or failure to complete treatment according to the course of treatment for other reasons.

2.2 Equipment and materials

The plasma exchange machine is produced by Beijing Weili company, and the plasma separator mpso5 is produced by Belk company. The exchange solution is 1000ml fresh frozen plasma and 20-40 g human albumin injection.

2.3 therapeutic method

Both groups were given comprehensive medical treatment, and the treatment group was added with plasma exchange. Specific methods:electrocardiographic monitoring, puncture and catheterization through femoral vein under sterile conditions to create extracorporeal circulation pathway. The plasma separator is aseptically connected with the circulating pipeline, and the arterial and venous ends of the cannula are connected with the artificial liver therapeutic instrument to start the treatment. Pre flush the pipeline with normal saline +heparin sodium, use about 1000ml of fresh frozen plasma each time,and supplement the patient with 20-40 g human albumin injection(according to the treatment needs). Thirty patients were treated with PE for 87 times. Six indexes of hemagglutination, liver function,IL-6, PCT and CRP were measured 4 hours after the treatment.

2.4 Test indicators, efficacy indicators and adverse reactions

2.4.1 Test indicators

(1) The levels of alt, AST, TBIL, ALB), PTA, IL-6, PCT and CRP were measured before and after treatment.

(2) The improvement degree of clinical manifestation of the two groups before and after treatment was observed.(3) Observe the occurrence of adverse reactions in the treatment group.

2.4.2 Efficacy index

Efficacy indicators include:(1)symptoms and signs: fatigue,anorexia, abdominal distension, oliguria, bleeding, hepatic encephalopathy, infection and peritoneal effusion; (2) Test indicators:TBIL, AST, alt, ALB, PTA

2.5 Efficacy criteria

The curative effect was evaluated 4 hours after the end of plasma exchange treatment [2], which was effective: the above symptoms and signs were significantly improved; The indexes of liver function were significantly improved, serum bilirubin decreased by more than 40%, PTA was more than 40% or INR was less than 1.5. Invalid:aggravation of symptoms and signs; Deterioration of liver function;New complications and or extrahepatic organ failure, or aggravation of existing complications.

2.6 Statistical processing

SPSS 26.0 software was used for statistics. The measurement data were expressed by mean ± standard deviation (±s). T-test was usedforcomparison beforeandaftertreatment.The counting data wereexpressedinpercentage.The χ2testwas used forcomparison between groups, and the difference was statistically significant(P＜0.05).

3. Results

3.1 Comparison of clinical efficacy

After the intervention of different treatment methods, the symptoms and signs of the two groups were improved. The total effective rate of the PE group was 80% (24/30) and that of the control group was 46.6% (14/30). The difference between the two groups was statistically significant. The curative effect of the PE group was better than that of the control group (Table 1).

Table 1 Comparison of efficacy between the control group and plasma exchange groupw[n (%)]

3.2 Comparison of liver function indexes and PTA between the two groups before and after treatment

After treatment, alt, AST, TBIL and ALB in the control group were lower than those before treatment, and PTA level was higher than that before treatment, which had no statistical significance (P＞0.05).The levels of alt, AST and TBIL in PE group were lower than those before treatment (P＜0.05), and the levels of PTA and ALB were higher than those before treatment (P＜0.05) (Table 2).

Table 2 Changes in the liver function and PTA of bath groups(n=30,±s)

Table 2 Changes in the liver function and PTA of bath groups(n=30,±s)

Group ALT(IU/L) AST(IU/L) TBiL(μmol/L) ALB(g/L) PTA(%)Contorol group before 346.28±102.44 500.89±333.73 285.30±148.37 33.46±7.73 28.71±8.38 after 162.21±137.63 160.79±139.73 277.81±200.34 33.27±6.90 33.60±16.01 t 7.501 5.062 0.204 0.158 -1.700 P 0.001 0.000 0.840 0.876 0.100 PE group before 418.14±280.75 288.08±230.30 295.32±123.35 33.27±5.78 27.87±11.79 after 127.56±102.50 101.42±96.34 147.55±112.31 35.64±4.63 55.69±20.82 t 5.104 4.452 7.071 -2.201 -7.842 P 0.001 0.001 0.000 0.036 0.000

3.3 Comparison of inflammatory factors between the two groups before and after treatment

The levels of IL-6, PCT and CRP in the control group and PE group increased before treatment, and there was no statistical significance.After treatment, the levels of IL-6, PCT and CRP in the control group decreased but were not statistically significant (P＞0.05). The levels of IL-6, PCT and CRP in the PE group were significantly lower than those before treatment (P＜0.05). After treatment, the levels of IL-6, PCT and CRP in PE group were significantly lower than those in the two groups (P＜0.05) (Table 3).

Table 3 Changes in the levels of IL-6、PCT、CRP of both groups(n=30,±s)

Table 3 Changes in the levels of IL-6、PCT、CRP of both groups(n=30,±s)

Group IL-6(pg/L) PCT(ng/mL) CRP(mg/L)Contorol group before 126.84±109.61 1.27±1.06 38.65±28.45 after 74.21±43.51 1.09±0.90 22.35±10.83 t 1.945 0.830 1.998 P 0.060 0.414 0.093 PE group before 29.30±26.50 2.08±1.57 20.23±19.17 after 12.16±10.84 1.04±0.85 8.63±6.25 t 2.406 4.567 2.709 P 0.027 0.001 0.018

3.4 Comparison of clearance rate of inflammatory factors between two groups after treatment

After treatment, the clearance rates of IL-6, PCT and CRP in the control group were lower than those in the PE group (P＜0.05) (Table 4).

Table 4 Comparison of inflammatory factor clearance roctes between the two groups after treatment(%,n=30,x ±s)

Table 4 Comparison of inflammatory factor clearance roctes between the two groups after treatment(%,n=30,x ±s)

Note: the indicators of IL-6, PCT and CRP are clearance rates; Clearance =(before treatment - after treatment) / before treatment × 100%

Group IL-6 PCT CRP Control group 34.31±14.43 30.03±23.75 25.76±7.50 PE group 67.08±25.84 68.84±19.51 43.62±17.68 t 3.174 4.780 2.651 P 0.004 0.000 0.016

3.5 Adverse reaction records of treatment group

In PE group, nausea occurred in 3 cases, hypotension occurred in 2 cases, and shivering occurred in 1 case. All cases were relieved after symptomatic treatment, and no serious adverse reactions occurred.

4. Discussion

Chronic and acute liver failure (CHF) is a syndrome of rapid deterioration of the original chronic liver disease caused by various acute pathogenic factors. Most of them are caused by infection,drugs, viruses and alcohol. Most of them rapidly progress to hepatic encephalopathy of more than 2 degrees in a short time. The mortality is high and the clinical prognosis is poor, up to 80%[3,4].The metabolism, detoxification, synthesis and immune functions of the liver are severely damaged during the onset of chronic acute liver failure, which gradually accumulates the body's metabolites and leads to the disorder of the body's microenvironment[5],and then leading to the progress of chronic acute liver failure. Therefore,it is of great significance to remove metabolic wastes, toxins and inflammatory mediators in patients with chronic and acute liver failure. At present, drugs are the most basic method for the treatment of chronic and acute liver failure, but the efficacy for some severe patients is limited [6].Therefore, it is necessary to treat chronic and acute liver failure with new adjuvant methods. As we all know,non bioartifical liver (nbal) support system has played an obvious role in the treatment of many acute severe diseases. Zhang Jian [7]ound that plasma exchange can improve liver and kidney function and coagulation indexes in patients with acute fatty liver during pregnancy, with good prognosis and high safety. Wushilang [8]believe that in patients with acute pancreatitis caused by hyperlipidemia,early use of plasma exchange can significantly improve the clinical symptoms, prevent the progress of the disease and prevent the occurrence of adverse prognosis.

Plasma exchange is the most widely used in Non-ecological artificial liver [9],For example, Rao Jieyu [10]believe that nursing intervention combined with plasma exchange in patients with liver failure can significantly improve their liver function and coagulation indicators, accelerate disease recovery and improve poor prognosis. Yu Tao[11]found that the use of plasma exchange in patients with liver failure can remove harmful substances from the body, restore the liver function of patients, and significantly improve the prognosis. Xu Hui[12]found that plasma exchange can remove inflammatory factors and toxic substances in patients with chronic and acute liver failure, promote liver function recovery and hepatocyte regeneration, and accelerate disease recovery. Plasma exchange can not only effectively remove toxins, bilirubin and some pathogenic factors in patients, but also supplement essential substances such as coagulation factors lacking in patients with chronic acute liver failure, and correct metabolic disorders caused by chronic acute liver failure[13].Cytokine storm is considered to be closely related to the degree of hepatocyte necrosis and the prognosis of the disease [14].IL-6 is a key pro-inflammatory factor in the process of chronic acute liver failure. The elevated level of IL-6 in patients with secondary infection of liver failure can not only cause a large number of inflammatory cells to gather in the liver, causing liver damage, but also lead to liver ischemia and hypoxia damage, aggravating liver failure [15]. Procalcitonin is closely related to infection. Wang chuanmin [16]found that the original value of serum calcitonin increased regardless of whether the patients with liver failure were complicated with infection, and was related to the severity of liver injury. ESR,as a protein synthesized and secreted by liver epithelial cells, is not only related to the severity of liver injury, but also can be used as a monitoring indicator for the dynamic changes of patients with chronic and acute liver failure. The more severe the liver injury, the higher the ESR, and is closely related to the prognosis of patients with chronic and acute liver failure. It can be used as an indicator to evaluate the prognosis of the disease [17,18].Therefore, the above three inflammatory factors were selected to evaluate the clinical efficacy and prognosis of plasma exchange in patients with chronic and acute liver failure.

The results of this study showed that alt, AST, TBIL, ALB, IL-6,PCT and CRP in the two groups decreased compared with those before treatment, and PTA increased with statistical significance(P＜0.05). The total effective rate in the treatment group was 80%,which was higher than that in the control group by 46.6%, with statistical significance (P＜0.05). The adverse reactions in the treatment group were mild, which could be relieved after treatment without causing serious adverse consequences. The results and efficacy were consistent with many research reports. In conclusion,the combination of drugs and plasma exchange can significantly reduce the clinical symptoms of patients with chronic and acute liver failure, improve liver function, inflammatory factors, coagulation function and other indicators, effectively prevent the further aggravation of liver inflammation. At the same time, the damage of inflammatory factors to liver function, prolong the survival period of patients, and buy time for liver transplantation for some patients in the later stage. In addition, the side effects of clinical application are small, and there are few serious complications, It can not only improve the prognosis of patients, but also improve the survival time.To some extent, it can buy time for patients with liver failure to wait for liver transplantation. However, due to the small sample size of this study, we can further explore the effect of plasma exchange on liver function, inflammatory factor clearance and disease prognosis in patients with chronic and acute liver failure by expanding the sample size in the later stage.

Description of the author's contribution:

lichuyi is responsible for writing the paper, Wen Xue is responsible for statistical data, Li Bin and Wang Junke is responsible for collecting cases and sorting out data, Weixiaojing is responsible for the operation of artificial liver plasma exchange, yuxiaohui is responsible for revising the paper and guiding the experiment, and all authors read and agree with the final text.

Conflict of interest: no conflict of interest for all authors