Portal hypertension - Treatment

Treatment of portal hypertension involves identifying and eliminating the cause of the disease. It may be more serious than portal hypertension. For example, hepatocellular carcinoma that invades the portal vein is a contraindication to active therapy of bleeding esophageal varices. If bleeding from varices is due to portal vein thrombosis in erythremia, before any surgical treatment, the platelet count is reduced by bloodletting or administration of cytostatics; anticoagulants may be required.

Preventive treatment of varicose veins is not indicated. Rupture of these veins may not occur, as collaterals develop over time.

In acute portal vein thrombosis, the thrombus usually has time to organize by the time treatment begins, so anticoagulant therapy is inappropriate. With timely diagnosis, the prescription of anticoagulants can prevent continued thrombosis.

With adequate treatment, including blood transfusions, children usually survive bleeding. Care should be taken to ensure that transfused blood is compatible and peripheral veins should be preserved if possible. Aspirin should be avoided. Upper respiratory tract infection should be treated vigorously because it contributes to bleeding.

Administration of somatostatin and sometimes the use of a Sengstaken-Blakemore catheter may be required.

Endoscopic sclerotherapy is the main method of emergency therapy.

In case of significant or recurrent bleeding, sclerotherapy can be used as a delayed measure. Unfortunately, it is not applicable to large varicose veins of the fundus of the stomach, so congestive gastropathy persists in such patients.

Surgery to reduce pressure in the portal vein is usually not possible because there are no veins suitable for bypass. Even veins that appear normal on venograms are unsuitable, mainly due to thrombosis. In children, the veins are very small and difficult to anastomose. The presence of many small collaterals also complicates the operation.

The results of all types of surgical interventions are extremely unsatisfactory. The least successful is splenectomy, after which the highest percentage of complications is observed. The most favorable results are obtained by shunting (portocaval, mesentericocaval, splenorenal), but it is usually not possible to perform it.

If, despite massive blood transfusions, blood loss progresses, it may be necessary to transect the esophagus and then restore it with a stapler. This method does not stop bleeding from gastric varices. In addition, the incidence of postoperative complications is significant. TIPS is usually not possible.

Bleeding from esophageal varices

Predicting the Gap

Within 2 years after the detection of liver cirrhosis, bleeding from varicose veins of the esophagus occurs in 35% of patients; 50% of patients die during the first episode of bleeding.

There is a clear correlation between the size of varicose veins visible during endoscopy and the likelihood of bleeding. The pressure inside the varicose veins is not so important, although it is known that for varicose veins to form and bleeding to occur, the pressure in the portal vein must be higher than 12 mm Hg.

An important factor indicating a high probability of bleeding is red spots that can be seen during endoscopy.

To assess the function of hepatocytes in cirrhosis, the Child criteria system is used, which includes 3 groups - A, B, C. Depending on the degree of hepatocyte dysfunction, patients are assigned to one of the groups. The Child group is the most important indicator for assessing the likelihood of bleeding. In addition, this group correlates with the size of varicose veins, the presence of red spots during endoscopy and the effectiveness of treatment.

Three parameters - the size of varicose veins, the presence of red spots and liver cell function - allow the most reliable prediction of bleeding.

In alcoholic cirrhosis, the risk of bleeding is highest.

The probability of bleeding can be predicted using Doppler ultrasound. In this case, the blood flow velocity in the portal vein, its diameter, the size of the spleen and the presence of collaterals are assessed. With high values of the congestion index (the ratio of the area of the portal vein to the amount of blood flow in it), the probability of early bleeding is high.

Prevention of bleeding

It is necessary to try to improve liver function, for example by abstaining from alcohol. Aspirin and NSAIDs should be avoided. Dietary restrictions, such as eliminating spices, as well as taking long-acting H2 blockers do not prevent the development of coma.

Propranolol is a non-selective beta-blocker that reduces portal pressure by constricting the vessels of the internal organs and, to a lesser extent, reducing cardiac output. It also reduces blood flow in the hepatic artery. The drug is prescribed in a dose that reduces the resting pulse rate by 25% 12 hours after administration. The degree of reduction in portal pressure varies among patients. Even high doses do not produce the expected effect in 20-50% of cases, especially in advanced cirrhosis. Portal pressure should be maintained at a level no higher than 12 mm Hg. Monitoring of hepatic vein wedge pressure and portal pressure determined endoscopically is desirable.

Child's classification of liver cell function in cirrhosis

Indicator	Child group
	A	IN	WITH
Serum bilirubin level, µmol/l	Below 34.2	34.2-51.3	Above 51.3
Serum albumin level, g%	Above 3.5	3.0-3.5	Below 3.0
Ascites	No	Easily treatable	Difficult to treat
Neurological disorders	No	Minimum	Precoma, coma
Nutrition	Good	Reduced	Exhaustion
Hospital mortality, %	5	18	68
One-year survival rate, %	70	70	30

Propranolol should not be prescribed for obstructive lung diseases. It may complicate resuscitation measures in the event of bleeding. In addition, it contributes to the development of encephalopathy. Propranolol has a significant first-pass effect, so in advanced cirrhosis, in which the liver's elimination of the drug is slow, unpredictable reactions are possible.

In particular, propranolol somewhat suppresses mental activity.

A meta-analysis of 6 studies suggests a significant reduction in bleeding but not mortality. A subsequent meta-analysis of 9 randomized trials found a significant reduction in bleeding with propranolol. Selecting patients for whom this treatment is indicated is difficult because 70% of patients with esophageal varices do not bleed. Propranolol is recommended for large varices and for red spots seen on endoscopy. If the venous pressure gradient is greater than 12 mmHg, patients should be treated regardless of the degree of venous dilation. Similar results have been obtained with nadolol. Similar survival rates and prevention of the first bleeding episode have been obtained with isosorbide-5-mononitrate. This drug may impair liver function and should not be used in advanced cirrhosis with ascites.

A meta-analysis of studies of prophylactic sclerotherapy found generally unsatisfactory results. There was no evidence that sclerotherapy was effective in preventing the first bleeding episode or improving survival. Prophylactic sclerotherapy is not recommended.

Diagnosis of bleeding

In the clinical picture of bleeding from varicose veins of the esophagus, in addition to the symptoms observed with other sources of gastrointestinal bleeding, symptoms of portal hypertension are noted.

The bleeding may be mild and may manifest as melena rather than hematemesis. The intestines may fill with blood before bleeding is recognized, even after several days.

Bleeding from varicose veins in cirrhosis adversely affects hepatocytes. This may be due to decreased oxygen delivery due to anemia or increased metabolic needs due to protein breakdown after bleeding. A decrease in blood pressure reduces blood flow in the hepatic artery, which supplies blood to the regenerative nodes, which may lead to their necrosis. Increased nitrogen absorption from the intestine often leads to the development of hepatic coma. Deterioration of hepatocyte function may provoke jaundice or ascites.

Bleeding not associated with varicose veins is also often observed: from a duodenal ulcer, gastric erosions, or with Mallory-Weiss syndrome.

In all cases, an endoscopic examination should be performed to identify the source of bleeding. An ultrasound scan is also required to determine the lumen of the portal and hepatic veins and to exclude a volumetric formation, such as hepatocellular carcinoma.

Based on a biochemical blood test, it is impossible to differentiate bleeding from varicose veins from ulcerative bleeding.

Forecast

In cirrhosis, mortality from variceal bleeding is about 40% for each episode. In 60% of patients, bleeding recurs before discharge from the hospital; mortality within 2 years is 60%.

The prognosis is determined by the severity of hepatocellular insufficiency. The triad of unfavorable signs - jaundice, ascites and encephalopathy - is accompanied by 80% mortality. The one-year survival rate in low-risk (Child groups A and B) is about 70%, and in high-risk (Child group C) - about 30%. The determination of survival is based on the presence of encephalopathy, prothrombin time and the number of units of blood transfused during the previous 72 hours. The prognosis is worse in alcoholic liver disease, since in it the impairment of hepatocyte function is more pronounced. Abstinence from alcohol significantly improves the prognosis. If chronic hepatitis remains active, the prognosis is also unfavorable. In primary biliary cirrhosis (PBC), bleeding is relatively well tolerated.

Survival is worse with low portal vein flow velocity as determined by Doppler ultrasound.

The importance of hepatocyte function is emphasized by the fact that when it is relatively preserved, for example in schistosomiasis, non-cirrhotic portal hypertension in India and Japan, and in portal vein thrombosis, the prognosis for bleeding is relatively favorable.

General medical treatment measures

When hospitalized for bleeding from esophageal varices, all patients undergo Child's liver function assessment. Bleeding may continue, so careful monitoring is necessary. If possible, it should be performed in an intensive care unit by specially trained personnel with in-depth knowledge of hepatology. The patient should be monitored from the very beginning by a therapist and a surgeon, who should agree on the treatment tactics.

Child-Pugh classification and hospital mortality from bleeding

Group	Number of patients	Hospital mortality
A	65	3(5%)
IN	68	12 (18%)
WITH	53	35 (68%)
Total	186	50 (27%)

Massive blood transfusions may be required. On average, 4 units are transfused in the first 24 hours, and up to 10 units over the entire hospital stay. Saline solutions should be avoided. Excessive circulating blood volume promotes recurrence of bleeding. Animal studies have shown that this is due to increased portal vein pressure caused by increased resistance in collateral vessels after bleeding.

There is a risk of coagulation factor deficiency, so freshly prepared blood, freshly prepared red blood cells, or freshly frozen plasma should be transfused whenever possible. Platelet transfusion may be required. Vitamin K should be administered intramuscularly.

Cimetidine or ranitidine are prescribed. Although their effectiveness in patients with severe hepatocellular failure has not been proven in controlled studies, they often develop stress-induced acute ulcers. With gastrointestinal bleeding in the context of cirrhosis, there is a high risk of infection, so antibiotics such as norfloxacin should be prescribed to suppress the intestinal microflora.

Sedatives should be avoided, and if necessary, oxazepam (nozepam, tazepam) is recommended. In alcoholics at risk of delirium, chlordiazepoxide (chlozepide, elenium) or hemineurin (clomethiazole) may be effective. If portal hypertension is caused by presinusoidal block and liver function is intact, the likelihood of hepatic encephalopathy is low and sedatives can be prescribed freely.

To prevent hepatic encephalopathy in cirrhosis, it is imperative to limit protein intake with food, prescribe lactulose, neomycin 4 g/day, aspirate the contents of the stomach and administer phosphate enemas.

In case of tense ascites, careful paracentesis and administration of spironolactone are acceptable to reduce intra-abdominal pressure.

Numerous methods or combinations of methods are used to treat bleeding varices. These include esophageal vein sclerotherapy (the "gold standard"), vasoactive drugs, Sengstaken-Blakemore catheters, TIPS, and emergency surgery. Controlled trials have failed to show a significant advantage for any one method, although all can stop bleeding from esophageal varices. The results of variceal vein sclerotherapy and vasoactive drugs are surprisingly similar.

Vasoactive drugs

Vasoactive drugs are used in acute bleeding from varicose veins to reduce portal pressure both before and in addition to sclerotherapy.

Vasopressin. The mechanism of action of vasopressin is to contract the arterioles of the internal organs, which causes an increase in resistance to blood flow to the intestine. This helps reduce bleeding from varicose veins by reducing pressure in the portal vein.

20 IU of vasopressin in 100 ml of 5% glucose solution is administered intravenously over 10 minutes. The pressure in the portal vein decreases for 45-60 minutes. It is also possible to prescribe vasopressin in the form of prolonged intravenous infusions (0.4 IU/ml) for no more than 2 hours.

Vasopressin causes contraction of coronary vessels. Before its introduction, an ECG should be taken. During the infusion, colicky abdominal pain may occur, accompanied by bowel movements and paleness of the face.

A temporary decrease in portal vein blood flow and arterial pressure promotes the formation of a clot in the damaged vein and stops bleeding. A decrease in arterial blood supply to the liver in cirrhosis is undesirable.

With repeated use, the effectiveness of the drug decreases. Vasopressin can stop bleeding, but it should only be used as a preliminary treatment before starting other methods. If bleeding is caused by clotting disorders, vasopressin is less effective.

Nitroglycerin is a potent venous and moderately active arterial vasodilator. Its use in combination with vasopressin reduces the number of blood transfusions and the frequency of esophageal tamponade, but the incidence of side effects and hospital mortality are the same as with vasopressin. In the treatment of bleeding from esophageal varices, nitroglycerin is administered intravenously (40 mg/min) or transdermally in combination with vasopressin at a dose of 0.4 IU/ml. If necessary, the dose is increased to ensure systolic blood pressure at a level of more than 100 mm Hg.

Terlipressin is a more stable and long-acting substance than vasopressin. It is administered intravenously by jet stream at a dose of 2 mg, and then 1 mg every 4 hours for 24 hours. The pressure in the varicose veins of the esophagus decreases, which helps stop bleeding.

Somatostatin affects smooth muscles and increases resistance in the arteries of internal organs, thereby reducing pressure in the portal vein. In addition, it inhibits the action of a number of vasodilator peptides, including glucagon. It causes a small number of serious side effects.

In a controlled study, the rate of recurrent bleeding was reduced by half compared to the placebo control group, and the rate of blood transfusion and esophageal tamponade was reduced by half. In patients with Child's group C, the drug was ineffective. In one study, somatostatin was better than vasopressin at stopping bleeding, while in another, the results were contradictory. Overall, somatostatin treatment is safe and as effective as sclerotherapy.

Intravenous infusion of the drug adversely affects blood circulation in the kidneys and water-salt metabolism in the tubules, so it should be administered with caution in ascites.

Octreotide is a synthetic analogue of somatostatin, sharing the same 4 amino acids with it. Its T1/2 is significantly longer (1-2 h). Octreotide has been shown to be as safe and effective as sclerotherapy in the treatment of acute bleeding from esophageal varices, but does not reduce the frequency of early recurrence of bleeding.

Planned sclerotherapy of esophageal veins

Planned sclerotherapy of esophageal varices is less effective than emergency sclerotherapy undertaken to stop bleeding. Injections are given at 1-week intervals until all varices are thrombosed. The frequency of recurrent bleeding is reduced.

Between 30 and 40% of varicose veins after sclerotherapy re-dilate each year. Repeated procedures result in fibrous esophagitis, in which the varicose veins are obliterated, but the varicose veins of the stomach enlarge and may bleed constantly.

Endoscopic ligation of varicose veins

The method used is no different from ligation of hemorrhoidal veins. The veins are tied with small elastic rings. A regular end-view gastroscope is inserted into the lower part of the esophagus and an additional probe is inserted under its control. The gastroscope is then removed and a ligating device is fixed to its end. After this, the gastroscope is reintroduced into the distal section of the esophagus, the varicose vein is identified and aspirated into the lumen of the ligating device. Then, by pressing on the wire lever attached to it, an elastic ring is put on the vein. The process is repeated until all varicose veins are ligated. From 1 to 3 rings are applied to each of them.

Sclerotherapy of varicose veins

Preventive	Emergency	Planned
Efficacy not proven	Experience required Stops bleeding Impact on survival (?)	Mortality from bleeding is reduced Numerous complications The patient's commitment to treatment is important Survival does not change

The method is simple and has fewer complications than sclerotherapy, although more sessions are required to ligate varicose veins. The most common complication is transient dysphagia; the development of bacteremia has also been described. An additional probe can cause perforation of the esophagus. Ulcers may subsequently develop at the sites where the rings are applied. The rings sometimes slip, causing massive bleeding.

Ring ligation is no less effective than sclerotherapy in stopping acute bleeding from esophageal varices, but is more difficult to perform in conditions of ongoing bleeding. It prevents repeated bleeding episodes but does not affect survival. This method can replace the generally more accessible endoscopic sclerotherapy only in specialized centers. It cannot be combined with sclerotherapy.

Emergency surgical interventions

With the introduction of sclerotherapy, vasoactive drugs, balloon tamponade and especially TIPS, surgical interventions are used much less frequently. The indication for them is mainly the ineffectiveness of all the listed treatment methods. Bleeding can be effectively stopped by emergency portocaval shunting. Mortality, as well as the incidence of encephalopathy in the postoperative period, are significant among patients in group C. If bleeding is massive and recurs after 2 sclerotherapy procedures, TIPS is the method of choice. Alternative treatment methods are emergency formation of a mesenteric-caval anastomosis, or imposition of a narrow (8 mm) portocaval shunt, or transection of the esophagus.

Emergency esophageal transection using a stapler

Under general anesthesia, an anterior gastrotomy is performed and the device is inserted into the lower third of the esophagus (Fig. 10-59). A ligature is applied directly above the cardia, which draws the esophageal wall between the head and body of the device. Then the esophageal wall is sutured and transected. The device with the excised esophageal wall is removed. The wound of the stomach and anterior abdominal wall is sutured. Transection of the esophagus with the device always makes it possible to stop bleeding. However, one third of patients die during hospitalization from liver failure. Transection of the esophagus with a suturing device has become a recognized method of treating bleeding from esophageal varices. The operative time is short, the mortality rate is low, and complications are few. The operation is not indicated for prophylactic or planned purposes. Within 2 years after the operation, varicose veins usually recur and are often complicated by bleeding.

Prevention of recurrent bleeding

Recurrent variceal bleeding develops within 1 year in 25% of patients in group A, 50% in group B, and 75% in group C. One possible method for preventing relapses is to administer propranolol. The first controlled study in a group of patients with alcoholic liver cirrhosis with large varicose veins and a satisfactory general condition revealed a significant decrease in the relapse rate. The data from other studies were contradictory, which is probably due to the type of cirrhosis and the number of alcoholic patients included in the study. Propranolol therapy is ineffective in decompensated cirrhosis. The later the treatment is started, the better the results, since patients from the highest risk group have already died by this time. In low-risk patients, the effectiveness of propranolol is no different from that of sclerotherapy. The use of propranolol reduces the risk of recurrent bleeding, but probably has little effect on survival, and is justified in portal gastropathy. The combination of nadolol and isosorbide mononitrate is more effective than sclerotherapy in reducing the risk of recurrent bleeding.

Routine sclerotherapy of esophageal varices is performed at weekly intervals until all veins are occluded. Three to five procedures are usually required and can be performed on an outpatient basis. Frequent endoscopic monitoring and repeated injections of drugs are not indicated after sclerotherapy because they do not increase survival. Sclerotherapy should be performed only if bleeding recurrs. Routine sclerotherapy of esophageal veins reduces the incidence of bleeding recurrence and the need for blood transfusions, but does not affect long-term survival.

If sclerotherapy is ineffective, shunting is used as an emergency measure - the formation of a portocaval or splenorenal shunt or TIPS.

Portosystemic shunting

Portosystemic shunting is performed to reduce portal vein pressure, maintain overall hepatic and, in particular, portal blood flow, and, most importantly, to reduce the risk of hepatic encephalopathy, which complicates portal hypertension. None of the currently existing shunting methods can fully achieve this goal. Patient survival is determined by the functional reserve of the liver, since after shunting, the liver-cell function deteriorates.

Portacaval shunting

In 1877, Eck performed the first portocaval shunt in dogs; it is currently the most effective method for reducing portal hypertension.

The portal vein is connected to the inferior vena cava either end to side with ligation of the portal vein, or side to side, without disrupting its continuity. The pressure in the portal and hepatic veins decreases, and the blood flow in the hepatic artery increases.

The end-to-side connection probably provides a greater reduction in portal pressure of approximately 10 mmHg. Technically, this procedure is easier to perform.

Currently, portocaval shunts are rarely applied because they are often complicated by encephalopathy. Reduced hepatic blood flow worsens liver function. This complicates subsequent transplantation of this organ. Portocaval shunts are still used after bleeding has stopped, with a good functional reserve of the liver, when it is not possible to monitor the patient in a specialized center, or if there is a risk of bleeding from varicose veins of the stomach. It is also indicated in the early stages of primary biliary cirrhosis, in congenital liver fibrosis with preserved hepatocyte function, and portal vein obstruction in the region of the liver porta.

After portocaval shunting, the likelihood of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome decreases.

When assessing the indications for bypass surgery, the following are important: a history of bleeding from esophageal varices, portal hypertension, preservation of the portal vein, age under 50 years, no history of hepatic encephalopathy, and Child's group A or B. In patients over 40 years of age, survival after surgery is lower and the incidence of encephalopathy is twice as high.

Mesentericocaval shunting

In mesenteric-caval shunting, a shunt made of Dacron prosthesis is sewn between the superior mesenteric and inferior vena cava.

The technique of the operation is simple. The lumen of the portal vein is not closed, but the blood flow through it becomes insignificant. Over time, the shunt often becomes occluded, after which recurrent bleeding is possible. The mesentericocaval shunt does not complicate liver transplantation in the future.

Selective "distal" splenorenal shunting

In selective splenorenal bypass, the varicose veins at the gastroesophageal junction are transected, and blood is directed through the short gastrosplenic veins into the splenic vein, which is anastomosed with the left renal vein. It was assumed that blood flow in the portal vein would be preserved, but this does not appear to be the case.

Preliminary results of the operation were satisfactory; mortality was 4.1%, encephalopathy rate was 12%, 5-year survival was 49%. A subsequent larger randomized study in patients with alcoholic liver cirrhosis found that mortality and encephalopathy rate did not differ from similar indicators in non-selective splenorenal shunting. More favorable results were obtained in non-alcoholic cirrhosis, especially in cases where varicose veins of the stomach were the main problem. In addition, the use of this method is justified in case of bleeding from varicose veins in schistosomiasis, non-cirrhotic portal hypertension with dilated splenic vein. The operation does not interfere with subsequent liver transplantation.

The technique of distal splenorenal bypass is complex, and there are few surgeons who can perform it.

General results of portosystemic shunting

In the low-risk group, the operative mortality rate is approximately 5%. In the high-risk group, it reaches 50%.

During surgery on a portal vein affected by a pathological process, the shunt often closes; this complication often ends in death, the cause of which is often liver failure.

With normal functioning of the end-to-side portocaval anastomosis, bleeding from varicose veins of the esophagus and stomach can be prevented.

After bypass, the venous collaterals of the anterior abdominal wall disappear, and the size of the spleen decreases. Endoscopy after 6-12 months does not reveal varicose veins.

If the shunt is non-selective, both portal pressure and hepatic blood flow are reduced. As a result, liver function deteriorates.

In the postoperative period, jaundice often develops due to hemolysis and deterioration of liver function.

Decreased portal pressure with persistently low albumin levels causes ankle edema. Increased cardiac output associated with heart failure may also play a role in its development.

The patency of the shunt is monitored using ultrasound, CT, MRI, Doppler ultrasound or angiography.

Hepatic encephalopathy may be transient. In 20-40% of cases, chronic changes develop, and in about a third of cases, personality changes. Their frequency is higher, the larger the diameter of the shunt. They are most likely to develop with the progression of liver disease. Encephalopathy is more common in elderly patients.

In addition, bypass surgery may be complicated by paraplegia due to myelopathy, parkinsonism, and symptoms of cerebellar damage.

Transjugular intrahepatic portosystemic shunt

Initial attempts to create intrahepatic portosystemic shunts in dogs and humans were unsuccessful because the communication created between the hepatic and portal veins using a balloon quickly closed. Maintaining the patency of the shunt was possible using an expanding Palmaz stent, which is installed between the intrahepatic branch of the portal vein and the branch of the hepatic vein.

Usually, TVPS is performed to stop bleeding from varicose veins of the esophagus or stomach. However, before resorting to this method of treatment, it is necessary to make sure that other methods, in particular sclerotherapy and the introduction of vasoactive drugs, have failed. If bleeding continues, the results are unfavorable. The procedure is performed under local anesthesia after premedication with sedatives. Under ultrasound control, the bifurcation of the portal vein is identified. The middle hepatic vein is catheterized through the jugular vein, and a needle is passed through this catheter into a branch of the portal vein. A guidewire is installed through the needle and the catheter is inserted through it. The needle is removed and the pressure gradient in the portal vein is determined. The puncture channel is dilated with a balloon, after which angiography is performed. Then a metal expanding balloon stent Palmaz or a self-expanding metal stent Wallstent with a diameter of 8-12 mm is inserted. The stent diameter is selected so that the portal pressure gradient is below 12 mm Hg. If portal hypertension persists, a second stent can be installed in parallel to the first one. The entire procedure is performed under ultrasound control. It lasts 1-2 hours. TIPS does not interfere with subsequent liver transplantation.

TIPS is a technically complex intervention. With sufficient experience of the personnel, it can be performed in 95% of cases. However, according to one study, technical difficulties, early recurrence of bleeding, stenosis and thrombosis of the shunt required repeated TIPS during one hospitalization of the patient in 30% of cases. In 8% of cases, even after repeated intervention, it was not possible to stop the bleeding.

The mortality rate when installing a stent is less than 1%, and the mortality rate within 30 days is from 3% to 13%. The intervention may be complicated by bleeding - intra-abdominal, biliary or under the liver capsule. Stent displacement is possible, and the Wallstent must be straightened to its previous state using a loop.

Infection often develops, which can lead to death. Antibiotics should be administered prophylactically. Renal failure may develop if renal function is impaired and after intravenous administration of a large amount of contrast agent. The steel mesh of the stent can damage red blood cells and cause intravascular hemolysis. If the stent is mistakenly placed in the right hepatic artery, liver infarction develops. Hypersplenism persists after bypass.

Stenosis and occlusion of the stent. Low pressure gradient between the portal and hepatic veins contributes to the development of occlusion. The most important reason for stent closure is low blood flow through it. It is important to monitor the patency of the stent dynamically. This can be done by conventional portography or Doppler and duplex ultrasound, which provide a semi-quantitative assessment of the functional state of the shunt. Shunt occlusion often leads to recurrent bleeding from varicose veins.

Early stent occlusion occurs in 12% of cases, is usually caused by thrombosis and is associated with technical difficulties during its installation. Late occlusions and stenosis are associated with excessive changes in the intima of the hepatic vein section connected to the stent. They are more common in patients of Child's group C. Stenosis and occlusion of the stent develop in a third of patients within 1 year and in two thirds within 2 years. The frequency of these complications depends on the effectiveness of diagnostics. In case of stent occlusion, its revision is performed under local anesthesia. The lumen of the stent can be expanded by percutaneous catheterization or another stent can be installed.

Stopping bleeding.TIPS results in a decrease in portal pressure by approximately 50%. If bleeding is caused by portal hypertension, it stops regardless of whether the bleeding vein is located in the esophagus, stomach, or intestine. This is especially important for bleeding that does not stop after sclerotherapy and occurs against the background of decreased liver function. TIPS is more effective in reducing the recurrence rate of bleeding than sclerotherapy, but its effect on survival is insignificant. The recurrence rate of bleeding after 6 months ranges from 5% to 19%, and after 1 year - 18%.

Encephalopathy after TIPS.The placement of a non-selective side-to-side portosystemic shunt causes a decrease in the portal blood supply to the liver, so liver function deteriorates after TIPS. Not surprisingly, the incidence of encephalopathy after this procedure is almost the same (25-30%) as after surgical portocaval shunting. In 9 of 30 patients with a stent, 24 episodes of hepatic encephalopathy were noted, and in 12% they developed de novo. The risk of developing hepatic encephalopathy depends on the patient's age, Child group, and shunt size. Encephalopathy is most pronounced during the first month after surgery. It decreases with spontaneous stent closure. It can be reduced by placing another smaller stent into a functioning intrahepatic stent. Resistant encephalopathy is an indication for liver transplantation.

The hyperdynamic type of blood circulation, characteristic of cirrhosis, worsens after TIPS. Cardiac output and circulating blood volume increase. Blood stagnation in internal organs is possible. If the patient suffers from concomitant heart disease, heart failure may develop.

Other indications: An intrahepatic stent placed in TIPS, which is a portosystemic shunt placed end-on, can reduce ascites in patients with Child B. However, in controlled trials it was no more effective than conventional treatments and did not improve survival.

In hepatorenal syndrome, TIPS improves the condition of patients and increases their chances of receiving a liver transplant.

TIPS is effective in ascites and chronic Budd-Chiari syndrome.

Conclusions. TVPS is an effective method for stopping acute bleeding from esophageal and gastric varices when sclerotherapy and vasoactive drugs are ineffective. Its use in recurrent bleeding from esophageal varices should probably be limited to cases of hepatocellular insufficiency in which liver transplantation is planned.

The method is technically complex and requires a certain amount of experience. Complications such as stent occlusion and development of hepatic encephalopathy prevent a lasting therapeutic effect. TIPS is a simpler method of treatment and causes fewer complications than surgical application of a portosystemic shunt. It can be expected that complications in the remote period after stent placement will be similar to those observed with surgical application of shunts.

Liver transplantation

In liver cirrhosis and variceal bleeding, the cause of death may not be the blood loss itself, but hepatocellular failure. In these cases, the only solution is liver transplantation. Survival after transplantation does not depend on whether sclerotherapy or portosystemic shunting was performed earlier. Survival after sclerotherapy followed by liver transplantation is higher than after sclerotherapy alone. This may be explained by the fact that patients with a lower risk were referred to transplantation centers. Unstoppable bleeding from varices and terminal liver disease are indications for organ transplantation.

A previously placed portocaval shunt technically complicates transplantation, especially if manipulations were performed on the liver hilum. Splenorenal and mesenteric-caval shunts, as well as TIPS, are not a contraindication to liver transplantation.

After transplantation, most of the hemodynamic and humoral changes caused by cirrhosis undergo regression. Blood flow in the azygos vein normalizes slowly, indicating a slow closure of the portal vein collaterals.

Pharmacological effects on portal vein blood flow

Portal hypertension syndrome is one of the manifestations of the hyperdynamic type of blood circulation with increased cardiac output and decreased peripheral resistance. In this syndrome, the activity of the autonomic nervous system changes significantly. The involvement of many hormonal factors indicates the possibility of pharmacological action on certain manifestations of portal hypertension. Theoretically, the pressure (and blood flow) in the portal vein can be reduced by reducing cardiac output, reducing blood flow by vasoconstriction of the internal organs, dilating the veins of the internal organs, reducing intrahepatic vascular resistance, or, finally, surgical portocaval shunting. It is necessary to strive to preserve the blood supply to the liver and its function, therefore, methods of reducing pressure by reducing vascular resistance are more preferable than by reducing blood flow.

Decreased cardiac output

Cardiac output can be reduced by blocking myocardial beta1-adrenergic receptors. Propranolol has some of this effect. Metoprolol and atenolol, cardioselective blockers, reduce portal vein pressure less effectively than propranolol.

Decreased blood flow through the portal vein

The use of vasopressin, terlipressin, somatostatin and propranolol, which cause vasoconstriction in internal organs, has already been discussed.

Portal and intrahepatic vasodilators

Smooth muscles of the portal vein contain beta ₁ -adrenoreceptors. Probably, the portosystemic collaterals are already maximally dilated, the muscular layer in them is poorly developed. They react to vasodilator stimuli less strongly than large veins. Serotonin causes significant contraction of the vessels of the portal system, acting through S2 receptors. The sensitivity of collaterals to serotonin may be increased. The serotonin inhibitor ketanserin causes a decrease in portal pressure in cirrhosis. Its wide use as an antihypertensive drug is hampered by side effects, including encephalopathy.

In liver cirrhosis, the tone of the muscles of the venous wall can also be affected. In isolated perfused liver, it has been shown that the increase in vascular resistance in the portal vein can be reduced by vasodilators, including prostaglandin E ₁ and isoprenaline. Apparently, their action is directed at contractile myofibroblasts. A decrease in portal pressure is possible with nitroglycerin, 5-isosorbide dinitrate or mononitrate and is probably due to systemic vasodilation. In addition, these drugs cause a slight decrease in intrahepatic resistance in isolated liver and in cirrhosis.

Verapamil, a calcium channel blocker, has been shown to reduce the portal vein pressure gradient and intrahepatic resistance. However, this effect could not be demonstrated when administered to patients with liver cirrhosis. In alcoholic cirrhosis, the sympathetic nervous system is overactive. Intravenous administration of clonidine, a centrally acting alpha-adrenergic receptor agonist, to patients with alcoholic liver cirrhosis resulted in a decrease in postsinusoidal vascular resistance. A decrease in systemic arterial pressure limits the use of this drug.

Conclusion: pharmacological control

The relationships among cardiac output, systemic resistance and flow, and portal resistance and flow are not easy to assess. There is a reciprocal relationship between hepatic arterial flow and portal flow - an increase in one causes a decrease in the other.

In the future, more suitable drugs for the treatment of portal hypertension can be expected.

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