![Ascites is the most common complication of decompensated cirrhosis. About 20% of patients with cirrhosis experience ascites when they first visit the doctor, and the 2-year mortality rate is about 50% [1]. Due to the existence of ascites, patients with cirrhosis are more likely t - DayDayNews](https://cdn-dd.lujuba.top/img/loading.gif)
Ascites is the most common complication of decompensated cirrhosis. About 20% of cirrhosis patients develop ascites when they first visit the doctor, and the 2-year mortality rate is about 50% [1]. Due to the existence of ascites, patients with cirrhosis are more likely to suffer from other complications such as bacterial infection, electrolyte disorders, , kidney damage, malnutrition, etc. [2]. Effective control of ascites is an important part of the treatment of cirrhosis. Patients with mild and moderate cirrhosis who respond to sodium limiting and diuretic treatment have a good prognosis, but 15% to 20% of patients with ascites with cirrhosis still have no response to large doses of diuretics, which is refractory ascites (RA), and the 1-year mortality rate of RA can be as high as 60% to 70% [3]. In the past five years, based on the progress of clinical and basic research, multiple guidelines for cirrhosis ascites at home and abroad have been updated. However, the diagnosis and treatment of cirrhosis ascites, especially RA, is still a hot and difficult issue in clinical practice, and requires comprehensive prevention and treatment of combined traditional Chinese and Western medicine. Traditional Chinese medicine treats cirrhosis ascites is a characteristic of our country. Traditional Chinese medicine treatment plays an important role in anti-hepatic fibrosis, promoting the regression of ascites, and preventing the recurrence of ascites. Combining traditional Chinese and Western medicine to diagnose and treat cirrhosis ascites has unique advantages [8].
15 Diagnosis of ascites with cirrhosis in combination with traditional Chinese and Western medicine
1.1 Diagnosis of ascites with cirrhosis
According to clinical history, symptoms, signs and imaging examinations, the diagnosis of ascites with cirrhosis is not difficult. Pay attention to differentiation from heart failure , tuberculosis peritonitis , malignant tumors and pancreatic diseases.
Abdominal ultrasound, abdominal CT and MRI examination can determine whether there is ascites, amount and source of ascites, determine the location of ascites, and be used for diagnostic abdominal puncture. Abdominal ultrasound has the advantages of non-invasive, inexpensive and simple operation, and is the most commonly used imaging examination method. Abdominal CT and MRI examination are more suitable for obese patients and patients with small amounts of ascites, and are not affected by intestinal qi.
should undergo diagnostic abdominal puncture after excluding contraindications for newly cirrhosis. Through laboratory analysis such as physical and chemical properties of ascites, microbiology and cytology , the nature of ascites can be clarified and potential infections can be detected in the early stage. Routine examinations in ascites laboratory include cell counting, classification, total protein and albumin quantification, etc. Ascites cell count and classification are the primary indicators for ascites detection. For example, neutrophil count of ascites is >250×106/L. Even if the patient has no symptoms, spontaneous bacterial peritonitis should be considered. The albumin level in
ascites reflects the osmotic pressure of ascites . The difference between it and the serum albumin level can indirectly reflect the osmotic pressure difference between serum and ascites. The calculated serum-ascite albumin gradient (SAAG) is still a widely recognized indicator for judging the source of ascites. Ascites with SAAG ≥11 g/L are portal hypertension and are commonly found in cirrhosis caused by various causes. Ascites with SAAG <11>[9]. The total protein of ascites is less than 15 g/L, which is a risk factor for the occurrence of spontaneous peritonitis [10], and the significantly increased C reactive protein and insulin-like growth factor levels in serum and ascites are of great value for the diagnosis of malignant ascites [11].
1.2 Grading and classification of ascites
According to the response to diuretics and whether spontaneous bacterial peritonitis and/or liver and kidney syndrome , cirrhosis ascites can be divided into two categories: simple type/uncompromised ascites and refractory type/compromised ascites [12]. Simple type ascites can be further divided into 3 levels according to the amount of ascites. RA refers to ascites that have no response to dietary sodium restriction and diuretic treatment, and cannot control the large amount of ascites (LVP) or are prone to recurrence. RA can be further divided into two categories: diuretic-resistant RA (treated with the maximum dose of diuretic that the patient can tolerate, and ascites still persist or relapse) and diuretic-refractory RA (uncontrollable adverse reactions to diuretics and the maximum dose of diuretics cannot be used), and the diagnostic criteria for RA has no significant changes compared with 20 years ago [6].
1.3 Traditional Chinese Medicine Diagnosis of Ascites of Cirrhosis
Ascites of Cirrhosis belongs to the category of Chinese medicine bloating diseases, and is mainly related to dysfunction of the liver, spleen and kidney.Swelling is mostly caused by accumulation, prolonged symptoms such as jaundice, , , and . The liver failure to relieve and discharge, spleen failure, and kidney failure are the key pathogenesis of bloating. Qi stagnation, blood stasis, and water stop are its basic pathological factors. The pathogenesis attributes are the basic deficiency and the actual situation, and the conflict between good and evil. The original deficiency is liver, spleen and kidney deficiency, or weak yang energy, or insufficient yin blood. Evil deficiency mostly refers to the mutual qi, blood, water, and poison. Clinical common symptoms such as qi stagnation and water stop, spleen deficiency and water stop, damp and hot water stop, blood stasis water stop, spleen and kidney yang deficiency and water stop, liver and kidney yin deficiency and water stop, etc. are [8, 13].
2 Advances in combination of traditional Chinese and Western medicine treatment for ascites in cirrhosis
2.1 Advances in western medicine treatment
2.1.1 Simple ascites
is restricted by the source of donors for liver transplantation, and complication-oriented drug treatment is still the mainstream of cirrhosis cirrhosis [14]. Usually, whether to be hospitalized for treatment is determined based on the amount of ascites in patients with cirrhosis and their accompanying diseases. There are more ascites in grade 1, no obvious symptoms, few other complications of cirrhosis, and are sensitive to diuretic treatment, and are generally treated in outpatient clinics; the clinical symptoms and signs of grade 2 and grade 3 ascites are obvious, and they are often accompanied by other complications of cirrhosis, and often require hospitalization.
2.1.1.1 Bed rest
Traditionally believes that patients with cirrhosis should try to rest bed as much as possible, because the upright position can increase plasma renin levels, leading to water and sodium retention. Bed rest can not only increase liver blood flow, but also inhibit the renin-angiotensin-aldosterone system and sympathetic nervous system , promote the excretion of urinary sodium and the sensitivity to diuretics. However, the 2018 Guidelines of the European Society of Hepatology [5] believes that there is no sufficient evidence to confirm the above hypothesis, so it is not necessary to force all patients with cirrhosis to rest in bed.
2.1.1.2 Dietary sodium limit
Dietary sodium limit should be treated as the basic treatment for ascites in all stages. Multiple guidelines recommend moderate sodium limit. Dietary sodium intake is controlled at 80~120 mmol/d (equivalent to 4~6 g of salt) to achieve negative sodium balance. Unless hyponatremia is present, water intake is generally not strictly restricted. We must strengthen education for patients, increase their compliance with sodium limit in diet, and conduct nutritional assessments to ensure calories and protein intake, so as to avoid malnutrition and sarcopenia [15] to the greatest extent.
2.1.1.3 Diuretic
For most patients with cirrhosis, the effect of sodium restriction is limited in dietary and diuretics must be taken to better control ascites. Aldosterone antagonists (such as spironolactone), loop diuretics (such as furosemide, torasemide , bumetanib) and vasopressin V2 receptor antagonists (such as trvaptan, rivaptan) are the main diuretic drugs currently used to treat cirrhosis ascites.
html grade 21 ascites or initial ascites, using aldosterone antagonists alone can produce sufficient diuretic reaction. The recommended starting dose is 40~80 mg/d of spironolactone, 1~2 times/d oral [4]. The efficacy of grade 2/3 ascites or recurrent ascites is better than the sequential use of both, and can reduce the incidence of hyperkalemia [4, 16]. The ratio of the doses of the two is generally 5:2, and the starting dose is: 80~100 mg of spironolactone + 40 mg/d furosemide. If the effect is not good, the dose of spironolactone and furosemide can be increased in 3 to 5 days until the maximum dose is reached (spironolactone 400 mg/d, furosemide 160 mg/d).Increased urine volume, body mass reduction, and abdominal circumference are the basic indicators for judging the effectiveness of diuretics. For patients with cirrhosis who do not have peripheral edema, a daily body mass reduction of 0.8~1.0 kg is more appropriate. [5]. The ratio of random urine sodium to urine potassium can better evaluate the response of diuretic treatment. Some domestic scholars [17] believe that when random urine Na/K is > 1.25~1.45, it indicates that the amount of sodium excretion in 24 hours is > 78 mmol. If the patient's body quality does not change, the patient should be asked to limit the sodium intake; if the random urine Na/K ≤1.25, it indicates insufficient urine sodium excretion, and the amount of diuretic should be appropriately increased. Some foreign studies [18] believe that the predicted value of Na/K value is between 1.8 and 2.5 is relatively high.
diuretics are only symptomatic treatment and cannot change the natural medical history of patients with cirrhosis and improve survival rates. At the same time, we should be wary of the side effects of diuretics, including hypovolemia, electrolyte disorders (hyponatremia, hypokalemia /hyperkalemia), male breast wombness, muscle spasm , acute renal injury and hepatic encephalopathy [6, 14]. For patients with ascites with cirrhosis who take diuretics, body mass and serum creatinine, serum sodium and urine Na/K values should be closely monitored. After obtaining a significant diuretic response, the diuretic should be gradually reduced to the minimum dose required to maintain the least ascites or no ascites to minimize adverse reactions.
Patients with ascites with cirrhosis have poor sodium limit and conventional diuretics, especially when accompanied by hyponatremia, vasopressin V2 receptor antagonist can be considered. Such drugs can selectively antagonize the vasopressin V2 receptor on the main cells of the kidney collector tube, thereby achieving hypotonic diuresis without affecting electrolyte balance [19]. A multi-center randomized controlled study of Phase II and Phase III by domestic scholars [20-21] shows that for patients with cirrhosis ascites who have not had the effect of combined treatment with spironolactone and furosemide, oral administration of tovaptan 15 mg/d or 7.5 mg/d for one week can significantly reduce body mass and abdominal circumference, improve hyponatremia, and produce good diuretic effects. The side effects are mild (including constipation, diarrhea, dry mouth and , thirst), and 7.5 mg/d is more suitable for Chinese patients. However, it should be noted that ptan drugs cannot improve the long-term survival rate of patients with cirrhosis and ascites, and excessive correction of hyponatremia may also lead to permeable demyelination. Therefore, this type of drug can only be used with caution in the short term (time ≤30 days), and close monitoring of [6, 19] is required.
2.1.2 Refractory ascites
2.1.2.1 LVP combined with albumin
Multiple domestic and foreign guidelines [4-7] recommends LVP combined with albumin as the first-line treatment for RA patients. RA patients with significant peripheral edema may need to undergo LVP repeatedly (≥2 times/week). When one LVP is > 8 L, the risk of post-puncture circulatory dysfunction (PPCD) is significantly increased. PPCD can lead to renal damage, diluted hyponatremia, hepatic encephalopathy and even death. Therefore, each LVP must be ≤8 L. The 2017 Ascites Guidelines for Hepatology Branch of the Chinese Medical Association [4] recommends that ascites should be released for each LVP of 4~5 L. Intravenous infusion of human albumin after LVP can prevent PPCD. Generally, 1 L of puncture and discharge fluid is combined with infusion of 6~8 g of albumin.
Repeated multiple abdominal punctures increase the patient's pain, while increasing the risk of infection and inducing PPCD. Continuous abdominal drainage can be used as an alternative therapy for LVP. Tube drainage can be regularly and quantitatively discharged (the first time the ascites is not more than 1000 mL, and then 1500~2000 mL of fluid is released every day, and human albumin is intravenously injected 10~20 g/d), which can avoid sharp changes in blood volume and effectively alleviate symptoms such as abdominal distension and loss of appetite. However, attention should be paid to the risks of detube and abdominal infection, and more prospective controlled studies are needed to clarify its safety and effectiveness [22]. In addition to maintaining colloidal osmotic pressure and expanding blood volume,
albumin also has many functions such as anti-inflammatory , anti-infection, anti-oxidative stress, and immunoregulation. It is a drug with important therapeutic value for decompensated cirrhosis. Several recent clinical studies [23-25] show that long-term use of albumin therapy in patients with decompensated cirrhosis/RA can increase the "effective albumin concentration" (the amount of protein with complete structure and function), significantly control ascites, reduce serious complications such as infection and liver and renal syndrome-acute renal injury, and prolong the overall survival of patients. There is still controversy over long-term use of albumin therapy, and it is necessary to use individual drugs and combine drugs in combination with national conditions and patient specific conditions.
2.1.2.2 Transjugate intrahepatic portal shunt (TIPS) and alpha pump
TIPS can significantly reduce portal venous pressure and reduce ascites. It can be used as a replacement treatment for frequent LVP in patients with RA and transitional treatment before liver transplantation [27]. The patient's liver reserve function was good (MELD score <18),> coated stent , and the smaller stent diameter (8~10 mm) were all important factors in improving the success rate of TIPS treatment and reducing complications (mainly hepatic encephalopathy). [6, 28].Alfapumpump® is a subcutaneous implantable battery-powered pump produced by Swiss . It can transport ascites from the peritoneal cavity to the bladder through catheter and eliminate ascites through urination. It is another alternative treatment for frequent LVP in RA patients, especially for RA patients who are not suitable for TIPS treatment (such as hepatic encephalopathy, MELD score ≥18/Child-Pugh Grade C, accompanied by cardiorenal insufficiency and malignant tumors, the elderly, etc.) [29]. In order to regulate the management of alfapumpump®, a European working group recently developed the application consensus of alfapumpump® [30]. As an invasive treatment method, the side effects of implanting alfapumpump® (acute renal injury, bacterial peritonitis and urinary tract infection , etc.) cannot be ignored.
2.1.2.3 Liver transplantation
Child-Pugh grade C or refractory ascites who cannot place TIPS should consider liver transplantation. The 2016 Liver Transplantation Guidelines of the European Society of Hepatology [12] suggests that liver transplantation should also be considered for patients with grade 2/3 ascites, because 71% of these patients have a survival period of more than 10 years after liver transplantation, and their prognosis is significantly better than that of Child-Pugh C-grade RA patients.
2.2 Progress in the treatment of combined traditional Chinese and Western medicine
2.2.1 Combination of disease and syndrome, stage treatment
The bloated Chinese medicine syndrome type shows the characteristics of stage changes in the disease [31]. Combination of disease and syndrome and stage treatment are the main modes of combined traditional Chinese and Western medicine for the treatment of cirrhosis and ascites [32]. In the early stages of bloating, most of them belong to Child-Pugh A/B. The pathogenesis of traditional Chinese medicine is related to the liver failure to relieve dispersion, qi stagnation and blood stasis, liver wood circulates the spleen, spleen loss of health and mobility, and water and dampness stop gathering in the abdomen. Therefore, in the early stages of bloating, it is mostly treated by the liver and spleen, focusing on eliminating evil to strengthen the positive [33]. In a narrow sense, the removal of evil mainly refers to promoting diuresis (including evacuation of water). In a broad sense, the removal of evil covers treatment methods such as promoting qi, promoting blood circulation, clearing heat, removing dampness, and softening hardness. Meta analysis was conducted on 16 clinical controlled studies published from 1998 to 2018. [34] showed that the effective efficiency of spleen-retaining and diuretic treatment combined with Western medicine for treating cirrhosis and ascites was higher than that of the conventional Western medicine treatment group, and the improvement of liver function indicators such as albumin and total bilirubin was better than that of the Western medicine group. A meta-analysis of 10 clinically controlled studies [35] found that the clinical efficacy of Wuling San for qi-relief and diuretic Wuling San combined with Western medicine for cirrhosis and ascites was better than that of the control group, and the incidence of adverse reactions was lower than that of the control group, and the improvement of Child-Pugh score was better than that of the control group. "If the blood is not good, water will be caused by it" is one of the key pathogenesis of the occurrence and development of bloating diseases. " Blood Syndrome Theory " points out: "But remove blood stasis, the phlegm and water will disappear by itself." Therefore, in the entire process of treating bloating, you should always pay attention to the use of blood circulation and diuretic methods, and pay attention to promoting blood circulation without damaging the body, nourishing blood without leaving blood stasis [36].
For the treatment of stubborn ascites, we should both eliminate evil and strengthen the good. First, we should pay attention to , blood circulation and blood stasis , and secondly, we should pay attention to attacking and drinking water. Ai Xiangying et al. [37] used Taohe Chengqi Decoction combined with Western medicine diuretic, albumin and intermittent abdominal puncture and fluid discharge to treat 29 cases of stubborn ascites with Qi stagnation and blood stasis. The course of treatment was 28 days. It was found that the decline in abdominal circumference, ascites depth, body mass, and portal vein inner diameter of the patients in the treatment group was significantly greater than that of the Western medicine control group, and no serious adverse reactions such as upper gastrointestinal bleeding, hepatic encephalopathy, and liver and kidney syndrome occurred. Professor Liu Chenghai's team [38] used " Shengji Zonglu " to treat 32 cases of stubborn cirrhosis ascites with " Shengji Zonglu " with the addition and subtraction of Tuduzi Buqi Pills combined with Western medicine diuretics + albumin. The treatment course was 14 days. The results showed that Tuduzi Buqi Decoction, which combined with conventional Western medicine therapy with Yiqi and Enjoy the Blood and Eliminate the lungs, helped the subsidence of cirrhosis RA, and did not increase the risk of renal function damage and electrolyte disorders, which confirmed the effectiveness and safety of Chinese medicine for zhushui on the basis of routine treatments such as albumin infusion in Western medicine.
Child-Pugh grades in the middle and late stages of bloating mostly belong to B/C grades, mainly because of liver, spleen and kidney deficiency and blood stasis and water stasis. At this time, the treatment should be based on the liver, spleen and kidney, and attention should be paid to strengthening the body (warming and nourishing the spleen and kidney yang qi or nourishing the liver, kidney yin blood), and promoting blood circulation and promoting diuresis [39].A meta-analysis [40] shows that the Wenyang Lishui prescriptions that have been used most frequently in the treatment of ascites in the past 20 years include Zhenwu Decoction, Fuzililing Decoction and Shipi Decoction. The Wenyang Lishui compound prescription combined with Western medicine routine is better than pure Western medicine treatment in terms of the overall effective treatment of ascites and improving liver function. Patients with advanced bloating may also experience liver and kidney yin deficiency due to long-term use of diuretics or water-treated drugs, or upper gastrointestinal bleeding, and water and blood stasis can also occur. Professor Li Xiuxian's team [41] was combined with Yiguan Decoction and cucurbitat and zhuling and zhuling and conventional treatment with Western medicine (halving diuretic + albumin 10~20 g/d + intermittent abdominal puncture and fluid discharge). The treatment was randomly controlled to treat 36 cases of liver and kidney yin deficiency cirrhosis. The course of treatment was 28 days. It was found that compared with routine treatment of Western medicine, the kidney-soft liver method can better improve the patient's liver function and promote the regression of ascites, and at the same time reduce the use of diuretics and avoid serious complications caused by large doses of diuretics.
2.2.2 External treatment method for traditional Chinese medicine
Patients with ascites with cirrhosis are often accompanied by portal hypertension gastrointestinal lesions, poor appetite, and prominent gastrointestinal symptoms. In addition, diet is prohibited after upper gastrointestinal bleeding. The above situations limit the application of oral Chinese medicine decoctions. Internal treatment of internal diseases is a major feature of traditional Chinese medicine treatment. External treatment methods such as traditional Chinese medicine preservation enema, Chinese medicine application of navel and acupuncture have opened up new ways to treat cirrhosis ascites.
Chinese medicine retains enema for administration through rectal treatment, achieving local hyperosmotic state of the mucosa and exerting a "dialysis-like effect"; by inhibiting the production and absorption of intestinal endotoxins, it helps to restore liver function and resolve ascites, while avoiding the stimulation of the gastric mucosa by bitter cold Chinese medicine. Traditional Chinese medicine retention enema usually chooses rhubarb , Yinchen , red peony , white peony , white and drugs to clear the viscera, clear heat and promote blood circulation, and protect the membrane and muscle-generating drugs [32, 42].
Chinese medicine applying to the navel is guided by meridian theory. The Chinese medicine powder is blended and applied directly to the umbilical Shenque acupoint . It plays a role through the penis of the skin or the meridian acupoints. It is often used to drink water, clear heat and diarrhea, warm yang and strengthen the body, promote blood circulation and promote qi and eliminate bloating, combine with spicy and fragrant products that can promote orifices, [43]. A multi-center randomized controlled trial led by Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine [44] studied the safety and effectiveness of the treatment of ascites with cirrhosis ( morning glory , cheqianzi, rhubarb, coix seed , Muxiang , Gansui ) in the treatment of ascites with cirrhosis. The main efficacy evaluation indicators are the depth of ascites, and the secondary indicators include abdominal circumference, body mass, urine volume, etc. The clinical research is underway and is expected to provide high-quality evidence for the treatment of ascites with Chinese medicine for cirrhosis.
3 Outlook
The advantages of combining traditional Chinese and Western medicine for treating cirrhosis are becoming increasingly prominent, but the combination of traditional Chinese and Western medicine concepts and methods still needs to be deepened. First of all, we should emphasize the holistic view of traditional Chinese medicine and the concept of "preventing disease", strengthen compliance with Western medicine's etiology treatment, improve traditional Chinese medicine's anti-fibrosis treatment, strengthen nutritional support, and improve patients' quality of life; traditional Chinese medicine treatment should be combined with internal and external treatment, or different external treatment methods should be used sequentially. Secondly, we should pay attention to learning and exploring the academic experience of famous old Chinese medicine, further optimize the Chinese medicine compound prescription, screen effective Chinese medicine compound prescriptions and easy-to-promote external treatment methods such as traditional Chinese medicine retaining enema and Chinese medicine applying to the navel, strengthen the unity and cooperation of Chinese and Western medicine liver disease doctors, select appropriate cases, scientifically design, standardize efficacy indicators, and carry out multi-center controlled research. Third, efforts should be made to implement high-quality real-world research (RWS). The key technologies for evidence-based medical evaluation are mostly based on the modern biomedical model, which cannot fully reflect the characteristics of traditional Chinese medicine, thereby affecting the quality and level of clinical research in traditional Chinese medicine. RWS is a continuation and supplementation of randomized controlled trials. The RWS model conforms to the characteristics of individualized diagnosis and treatment and overall efficacy evaluation in traditional Chinese medicine. Without violating the individualized intervention of dialectical treatment, using the clinical data of traditional Chinese medicine for actual diagnosis and treatment, through strict and standardized design, measurement and evaluation, high-quality real clinical evidence can be obtained [45].RWS is expected to open up a new path for the evaluation of the efficacy of traditional Chinese medicine syndrome differentiation treatment, providing more high-quality scientific basis for the treatment of cirrhosis ascites with combined traditional Chinese and Western medicine, and finally forming a diagnosis and treatment plan for combined traditional Chinese and Western medicine cirrhosis ascites with Chinese characteristics .
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Citations in this article
Wang Lei. Combined diagnosis and treatment of ascites in cirrhosis [J]. Journal of Clinical Hepatobiliary Diseases , 2022, 38(9): 1956-1961.
Editor: Ge Jun
Official Account Editor: Xing Xiangyu
First release on the entire network｜Journal of Clinical Hepatobiliary Diseases》2022 Issue 9 "Integrated Treatment of Cirrhosis and Its Main Complications" Key Number (Executive Editor: Liu Ping)
Comments｜Liu Ping: Research Progress in Integrated Treatment of Traditional Chinese and Western Medicine in Cirrhosis
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