Non-invasive diagnosis of cirrhosis and the natural history of its complications

Several methods have been studied in the attempt to reach a diagnosis of cirrhosis by non-invasive means. Although abdominal ultrasound can detect the hepatic and extra-hepatic changes consistent with cirrhosis, its ability to distinguish chronic hepatitis from compensated cirrhosis is limited. Serum markers can rule in or rule out fibrosis in up to 35% of patients but, in individual patients, cannot differentiate the stages of fibrosis reliably. Transient elastography (Fibroscan) might be of value for the non-invasive diagnosis of cirrhosis; however, its reproducibility needs to be further validated. Cirrhosis can be divided into 4 stages: stage 1, no varices, no ascites; stage 2, varices without ascites and without bleeding; stage 3, ascites+/-varices; stage 4, bleeding+/-ascites. Yearly mortality ranges from 1% in stage 1 to 57% in stage 4. The yearly incidence of oesophageal varices is 5-7%; their rate of enlargement is 10-12% per year. The incidence of variceal bleeding is about 25% at 2 years. Bleeding stops spontaneously in about 50% of cases but early rebleeding occurs in 30-40% of patients. Bleeding-related mortality has declined over time and is now around 20% at 6 weeks.     

The natural history of HCV-related cirrhosis and its temporal progression across the different clinical stages

Purpose

The clinical course of hepatitis C virus-related cirrhosis and its temporal progression across the different clinical stages has not been completely investigated. Our study evaluated the cumulative incidences (CIs) of clinical outcomes marking disease progression across the different clinical stages.

Methods

At baseline, 660 patients were classified as compensated [absence (294), or presence (108) of gastroesophageal varices] or decompensated [ascites (144), variceal bleeding alone (45) or in combination with ascites (17) and encephalopathy alone or together with bleeding and/or ascites (52)]. Subjects were followed for 312 weeks to identify time to a first event marking disease progression.

Results

Among compensated patients without varices, the 312-week CIs for developing varices, ascites, and encephalopathy were 37.4, 13.6 and 3.5 %, respectively. The 312-week CIs of development of ascites, bleeding and encephalopathy were 24, 12.5 and 9.9 % for compensated subjects with varices, respectively. Among patients with ascites, the 312-week CIs of bleeding, liver-related deaths/transplant and encephalopathy were 23.5, 27.8, and 47.3 %, respectively. The 312-week CIs of ascites, liver-related deaths/transplant and encephalopathy were 22.5, 14.7 and 5.7 % among patients with bleeding; however, CIs of liver-related deaths were significantly higher in those with ascites plus bleeding (77.6 %). Patients with encephalopathy alone or in combination with ascites and/or bleeding displayed the highest rates of deaths (312 weeks, 90 %).

Conclusions

Among compensated patients, the presence of varices suggests a more accelerated course of the disease. Decompensated patients show the most severe clinical course, particularly in those with a combination of two or more clinical events.     

Non-invasive predictors of the presence of large oesophageal varices in patients with cirrhosis

BACKGROUND/AIMS: The usual clinical practice is to screen all patients with established cirrhosis at the time of diagnosis by upper endoscopy for the presence of varices. Patients with large varices should be treated with non-selective beta blockers to reduce the incidence of first variceal bleeding. However, fewer than 50% of cirrhotic patients have varices at screening endoscopy and most have small sized varices, with a low risk of bleeding. The aim of the present study was to determine whether clinical or laboratory non-endoscopic parameters could predict the presence of large oesophageal varices. PATIENTS/METHODS: Seventeen variables considered relevant to the prevalence of oesophageal varices were tested in 184 patients with cirrhosis, who underwent screening endoscopy. Small varices were regarded as those which flatten with insufflation or slightly protrude into the lumen, while large varices are those which protrude into the lumen or touch each other. None of the patients was on beta blockers or other vasoactive drugs or had a history of variceal bleeding. RESULTS: Oesophageal varices were present in 92 patients (50%), and large varices in 33 patients (17.9%).Variables associated with the presence of large oesophageal varices on univariate analysis were the presence of ascites and splenomegaly either by clinical examination or by ultrasound (p < 0.01), the presence of spiders (p = 0.02), platelet count (p < 0.0001), and bilirubin (p = 0.01). Factors independently associated with the presence of large oesophageal varices on multivariate analysis were platelet count, size of spleen and presence of ascites by ultrasound. Using mean values as cut-off points, it is noteworthy that only five out of 39 patients (12.8%) with platelets > or = 18(x 10(9)/l), spleen length < or = 135 mm and no ascites had varices. Moreover, all these patients had small sized varices. On the other hand, 15 out of 18 patients (83.3%) with a platelet count < 118 x 10(9)/l, spleen length > 135 mm and ascites had varices. Moreover, five out of those 18 patients had large varices (28.3%). CONCLUSION: Thrombocytopenia, splenomegaly and ascites are independent predictors of large oesophageal varices in cirrhotic patients. We suggest that endoscopy could be avoided safely in cirrhotic patients with none of these predictive factors, as large varices are absent in this group of patients.     

乙型肝炎肝硬化患者发生食管胃静脉曲张破裂出血的危险因素分析

目的探索乙型肝炎肝硬化患者发生食管胃静脉曲张破裂出血的危险因素。方法选取2014年10月—2016年6月因乙型肝炎肝硬化并发食管胃静脉曲张来我院进行治疗的患者165例,根据就诊当天是否发生破裂出血分为出血组和非出血组,分析该类患者破裂出血的危险因素。结果单因素分析结果显示:2组患者在年龄、性别和WBC计数方面的差异无统计学意义(P0.05),出血组患者HGB、PT明显高于非出血组,而PLT明显低于非出血组,差异有统计学意义(P0.05);出血组患者中肝功能Child-Pugh评分C级患者、重度食管胃静脉曲张患者及中重度腹水患者明显多于未出血组,2组患者在肝功能Child-Pugh评分、食管胃静脉曲张和腹水严重程度上的差异有统计学意义(P0.05)。多因素分析结果显示:肝功能Child-Pugh评分、PLT、腹水、门静脉内径和感染是发生破裂出血的危险因素,其中腹水严重程度是最主要的独立危险因素。结论肝功能Child-Pugh分级较低、PLT较低、腹水较严重、门静脉内径较大和出现感染是乙型肝炎肝硬化患者发生食管胃静脉曲张破裂出血的危险因素,临床上须尽早进行对症治疗,预防破裂出血的发生。     

Varizenblutung bei Patienten mit Leberzirrhose

In patients with cirrhosis, portal hypertension induces the development of portosystemic collaterals. Bleeding from these collateral vessels, however, only develops if the portosystemic pressure gradient is below 12 mmHg. Portal hypertension in cirrhosis is mediated by an increased intrahepatic resistance of the liver on the one hand and by an increase in the portal tributary blood flow on the other. Consequently, therapy can aim to reduce intrahepatic resistance or mesenteric blood flow (shunts, pharmacologic therapy) or can act locally on the source of bleeding itself (endoscopic therapy). Four aims can be defined: (1) inhibition of the development of varices, (2) prevention of the first bleeding episode when varices already exist, (3) therapy of the acute bleeding episode, and (4) prevention of recurrent bleeding.     

A case of liver cirrhosis due to hepatits C virus infection complicating giant anorectal varices treated with balloon-occluded retrograde transvenous obliteration

A 73-year-old man with liver cirrhosis due to hepatitis C virus infection was admitted to our hospital because of massive bleeding from external varices. Colonoscopic examination revealed that giant anorectal varices had developed between the anus and rectal ampulla, and had ruptured at the perianal site. On three-dimensional computed tomography imaging, the feeding and drainage vessels of the varices were identified as the inferior mesenteric vein and right inferior hemorrhoidal vein, respectively. Endoscopic therapies were not employed for the bleeding varices, because the blood flow volume of the feeding vessel was extremely large. Balloon-occluded retrograde transvenous obliteration (B-RTO) was therefore carried out through the drainage vessels. The variceal blood flow disappeared after B-RTO therapy, and the varices decreased in size with thrombus formation verified by colonoscopy. Bleeding from the external varices also ceased. B-RTO therapy may be an effective approach for giant anorectal varices presenting as a complication in liver cirrhosis patients in whom the main drainage vessels can be determined.     

Portal and mesenteric thrombosis associated with protein S deficiency]

INTRODUCTION: liver cirrhosis is the main cause of portal thrombosis (PT), while hypercoagulability syndromes are rarely found as the etiology of PT. We report a case of portal and mesenteric thrombosis secondary to protein S deficiency. CASE REPORT: a 74-year-old woman was admitted with melena secondary to upper gastrointestinal bleeding. She reported mild, diffuse abdominal pain in the last 2 weeks. Endoscopy revealed ruptured esophageal varices. Doppler ultrasonography and CT demonstrated a heterogeneous liver, splenomegaly and ascites, and complete non-occlusive PT involving the hilum and portal branches, as well as the superior mesenteric vein, with portosystemic collaterals. At this point a complete study for cirrhosis etiologies was negative, including a liver biopsy that showed nonspecific architectural changes secondary to diminished blood flow, which suggested non-cirrhotic portal hypertension. The search for hypercoagulability states determined a deficiency of S protein, with total pS = 107% and free pS = 56%. The patient was started on anticoagulant treatment and no other thrombotic events occurred. DISCUSSION: PT usually manifests without specific symptoms. The most common presentation is upper gastrointestinal bleeding, as occurred in our patient. Liver cirrhosis is one of the most frequent cause of PT. Up to 65% of these patients present an associated prothrombotic state, including protein S deficiency. Our case reminds us of the importance of a systematic search for hipercoagulability syndromes in patients with TP, even when the etiology can be conferred to liver cirrhosis.     

Complications of liver cirrhosis

The occurrence of complications increases the mortality in patients with cirrhosis of the liver. Therefore, early detection and treatment of complications of cirrhosis is of major importance. Following diagnosis of cirrhosis, a screening gastroscopy detects esophageal varices. Primary prevention of variceal bleeding can be initiated with β-receptor antagonists or variceal band ligation. With the first episode of ascites or the manifestation of other complications of cirrhosis such as hepatic encephalopathy and hepatorenal syndrome, a paracentesis excludes spontaneous bacterial peritonitis. Hepatorenal syndrome can be treated with a combination of vasopressors and albumine. Furthermore, occurrence of complications in patients with cirrhosis of the liver should prompt the evaluation of an indication for liver transplantation.     

Komplikationen der Leberzirrhose

The occurrence of complications increases the mortality in patients with cirrhosis of the liver. Therefore, early detection and treatment of complications of cirrhosis is of major importance. Following diagnosis of cirrhosis, a screening gastroscopy detects esophageal varices. Primary prevention of variceal bleeding can be initiated with ??-receptor antagonists or variceal band ligation. With the first episode of ascites or the manifestation of other complications of cirrhosis such as hepatic encephalopathy and hepatorenal syndrome, a paracentesis excludes spontaneous bacterial peritonitis. Hepatorenal syndrome can be treated with a combination of vasopressors and albumine. Furthermore, occurrence of complications in patients with cirrhosis of the liver should prompt the evaluation of an indication for liver transplantation.     

Clinical significance of variceal hemorrhage in recent years in patients with liver cirrhosis and esophageal varices

BACKGROUND AND AIMS: Recent progress in the treatment of variceal bleeding might have reduced the impact of variceal bleeding on survival in patients with esophageal varices. We conducted a retrospective cohort study in an attempt to re-evaluate the clinical significance of variceal bleeding. METHODS: A cohort of 304 patients with liver cirrhosis and esophageal varices, who had no previous history of variceal bleeding and no prophylactic therapy, was studied. RESULTS: During a median follow-up period of 32 months, 55 patients (18%) bled from varices and 111 (37%) died. Variceal hemorrhages accounted for 15% of total deaths. The mortality of first variceal bleeding was 25% in the whole group, but was remarkably different depending on liver function at the time of bleeding (0% in grade Child A vs 55% in grade C; P < 0.05). Among the survivors of first bleeding, 30% experienced rebleeding. Form of varix, red color sign and heavy drinking were the independent risk factors for first variceal bleeding. Multivariate analysis revealed that variceal bleeding still had a significant (P < 0.001) impact on death in the whole cohort, when other independent prognostic factors such as age, ascites, encephalopathy, platelet count, serum albumin level and hepatocellular carcinoma were adjusted. Furthermore, in subgroup analyses, variceal bleeding was more strongly (P < 0.001) linked to death in patients with alcoholic cirrhosis than in those with non-alcoholic cirrhosis, and showed a significant association with survival only for the patients in Child grade B. CONCLUSIONS: Variceal bleeding has various prognostic impacts depending on the etiology of cirrhosis or on the degree of liver dysfunction, and this needs to be taken into account in the prophylaxis against first variceal bleeding.     

Spleen size and portal hypertension in cirrhosis.

In 210 patients with cirrhosis of the liver there was no correlation between spleen size and the rise in portal pressure, whether measured directly or assessed clinically from the size of varices on barium swallow and the presence of ascites. Despite this, there was a correlation between the occurrence of bleeding as a presenting symptom and the size of varices assessed radiologically.     

Fibreoptic endoscopy and the use of the Sengstaken tube in acute gastrointestinal haemorrhage in patients with portal hypertension and varices.

The value of emergency upper gastrointestinal fibre-endoscopy, followed where required by the use of a modified Sengstaken tube, was studied during 84 episodes of acute bleeding in 75 patients who had evidence of portal hypertension with varices. The portal hypertension was due to alcoholic cirrhosis in 80% and to cryptogenic cirrhosis in 9% of the patients. By definition, varices were present in all patients, but in only 66% of episodes were the varices the cause of the bleed. The correct diagnosis of the source of bleeding was made at endoscopy in 89%. A Boyce modification of the Sengstaken-Blakemore tube was passed in 73% of the episodes of variceal bleeding. It effectively stopped the bleeding primarily in 85% of patients but was successful as a final definitive measure only in 46%. Furthermore, only 40% of the patients in whom the tube was passed, survived. Mortality rate could be related to the severity of the bleed and to hepatocellular dysfunction. Survival increased from 23% in those patients with jaundice, ascites, and encephalopathy on admission to 92% in those without these manifestations. The in-hospital survival rate was 52% in patients bleeding from varices and 64% in those bleeding from other causes, with an overall survival rate of 56%, indicating the poor prognosis in cirrhotic patients with gastrointestinal bleeding, irrespective of the cause.     

Abdominal bleeding due to spontaneous mesenteric vein rupture

Hepatic cirrhosis is the leading cause of portal hypertension and is usually associated with the development ofsplacnic varices. Variceal intraabdominal rupture is a rare cause of hemoperitoneum. A case of spontaneous mesenteric vein rupture is reported. CLINICAL CASE: 43-year-old man with hepatic cirrhosis (Child-Pugh C stage) and previous bleeding of esophageal varices, admitted to hospital because of orthostatic hypotension episodes (positive tilt test) and abdominal distention. Laboratory: anemia, low platelet count and abnormal coagulation tests. CT scan showed abdominal fluid. Exploratory laparotomy was performed and 3 liters of blood were found into the abdominal cavity. The mesenteric vein had a ruptured variceal dilatation with intermitent jet bleeding. No organ abnormalities were found. Repair of the dilated vein was performed. The patient evolved well and was dismissed from hospital ten days after admittance. OBJECTIVE: To present a case in which a rare cause of intraabdominal bleeding, usually associated with high mortality rate, is follawed by a good clinical evolution.     

Prognostic Indicators of Survival in Patients with Cirrhosis and Esophageal Varices, without Previous Bleeding

Sixty-one patients with cirrhosis with varices without previous bleeding were admitted to our Department over a period of 2 yr. Fifty had alcoholic cirrhosis. Child-Turcotte-Pugh class was A in 11 patients, B in 30, and C in 20. Varices were F1 in 18, and F2-F3 in 43. During follow-up of up to 40 months, one patient was lost to follow-up and 22 patients died, seven of gastrointestinal bleeding and 15 of liver failure. The probability of death from any cause was significantly related to Child-Turcotte-Pugh class, ascites, encephalopathy, s-albumin, s-bilirubin, prothrombin index, and galactose elimination capacity. Independent prognostic variables according to Cox's model resulted s-albumin, s-bilirubin, encephalopathy, and varices. Considering only patients who died from liver failure, survival was univariately related to the same determinants, whereas the Cox's model individuated s-bilirubin, s-albumin, ascites, and galactose elimination capacity as independent prognostic indicators. Considering only patients who died from gastrointestinal bleeding no Cox model could be performed due to the small number of deaths. In patients with F1 varices, the probability of death from liver failure was 5 times higher than that from gastrointestinal bleeding; in patients with F2-F3 varices, liver failure and gastrointestinal bleeding each accounted for approximately half of the deaths. These data could become useful when programming a clinical trial of prophylaxis which considers reduction in mortality as the main end-point.     

Editorial: Beta-blockers and the prevention of decompensation in cirrhosis: worth the trouble

Non-selective beta-blockers have been a cornerstone of therapy for prevention of esophageal variceal bleeding in cirrhosis patients for more than two decades. When lowering the hepatic vein portal pressure gradient (HVPG) below 12?mm?Hg or decreasing the pressure by 20% from baseline, these drugs are of proven benefit in reducing variceal bleeding and improving survival in this patient population. The recent work by Hendández-Gea et al., suggests that initiation of the beta-blocker nadolol in cirrhosis patients with high-risk varices can delay or prevent the first occurrence of clinically evident ascites. This finding comes with some caveats, however. The beneficial effect was only seen in patients who had an improvement by 10% or more from baseline HVPG pressure (only 51% of the treated patients in this study). This class of medications has some risk and tolerance issues, and many patients do not respond, even when the heart rate is optimally decreased. Despite this, the use of beta-blockers may be beneficial in the primary prevention of the formation of ascites and further decompensation of cirrhosis.     

Primary and secondary prophylaxis of esophageal variceal bleeding

Cirrhosis is a chronic condition with high-mortality. Portal hypertension (PH) is the initial and main consequence of cirrhosis and is responsible for most of its complications, including esophageal varices. A portal pressure, as determined by the hepatic venous pressure gradient (HVPG) >5 mm Hg defines PH. When the HVPG reaches 10 mm Hg or greater, the patient with compensated cirrhosis has developed clinically significant PH and is at a higher risk of developing varices and clinical decompensation. Patients with varices that have not bled are still in the compensated stage but are at a higher risk of decompensation than those without varices. Variceal hemorrhage constitutes a decompensating event, but its mortality differs whether it presents as an isolated complication of cirrhosis (20% 5-year mortality) or whether it presents in association with other complications (more than 80% 5-year mortality). While in the past, emphasis had been placed on managing the direct complications of PH, varices and variceal hemorrhage, it is now clear that these complications cannot be considered in an isolated manner. Rather, they should be considered in the context of advances in the staging of cirrhosis and other complications of cirrhosis that might occur concomitant or subsequent to the development of varices and variceal hemorrhage.     

A case of liver cirrhosis with bleeding from stomal varices successfully treated using balloon-occluded retrograde transvenous obliteration

A 66-year-old male patient with liver cirrhosis because of alcohol intake underwent a Hartmann’s procedure for rectal cancer. Four months later, bleeding from the sigmoid stoma occurred and persisted for 2 months. A colonoscopic examination revealed bleeding from stomal varices. Three-dimensional computed tomography (CT) imaging demonstrated the inferior mesenteric vein and left superficial epigastric vein as the feeding and drainage vessels, respectively. Balloon-occluded retrograde transvenous obliteration (B-RTO) through the left epigastric vein was performed using a microballoon catheter inserted from the right femoral vein according to the Seldinger method. A CT examination performed 2 days after the B-RTO procedure revealed that the blood flow had disappeared, with thrombosis formation in both the stomal varices and the feeding vein. No recurrent bleeding from the stoma occurred. B-RTO using a microballoon catheter is useful as a therapeutic procedure for stomal varices to prevent bleeding, since the procedure can be performed with minimal invasion using the Seldinger method.     

Cost-effectiveness analysis of beta-blockers vs endoscopic surveillance in patients with cirrhosis and small varices

AIM:To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.METHODS:A stochastic analysis based on decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices(Strategy 1)with that of endoscopic surveillance followed by beta-blockers treatment when large varices are demonstrated(Strategy 2),for preventing variceal growth,bleeding and death in patients with cirrhosis and small esophageal varices.The basic nodes of the tree were gastrointestinal endoscopy,inpatient admission and treatment for bleeding,as required.All estimates were performed using a Monte Carlo microsimulation technique,consisting in simulating observations from known probability distributions depicted in the model.Eight-hundred-thousand simulations were performed to obtain the final estimates.All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis,to assess the impact of the variability of such estimates on the outcome distributions.RESULTS:The event rate(considered as progression of varices or bleeding or death)in Strategy 1[24.09%(95%CI:14.89%-33.29%)]was significantly lower than in Strategy 2[60.00%(95%CI:48.91%-71.08%)].The mean cost(up to the first event)associated with Strategy 1[823￡(95%CI:106￡-2036￡)]was not significantly different from that of Strategy 2[799￡(95%CI:0￡-3498￡)].The cost-effectiveness ratio with respect to this endpoint was equal to 50.26￡(95%CI:-504.37￡-604.89￡)per event avoided over the four-year follow-up.When bleeding episodes/deaths in subjects whose varices had grown were included,the mean cost associated with Strategy 1 was 1028￡(95%CI:122￡-2581￡),while 1699￡(95%CI:171￡-4674￡)in Strategy 2.CONCLUSION:Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices.     

Portal hypertension: a permissive factor only in the development of ascites and variceal bleeding

It is controversial whether the occurrence of ascites and gastrointestinal bleeding in cirrhosis is related to the severity of portal hypertension. Portal pressure was examined in 124 unselected patients with portal hypertension due to chronic liver disease to evaluate this issue. Portal pressure was less in patients without complications of chronic liver disease (11.7 +/- 3.0 mmHg, n = 16) as compared to patients who had bled from varices or erosive gastritis (16.6 +/- 3.4 mmHg, p less than 0.001, n = 49), who had ascites (16.2 +/- 3.0 mmHg, p less than 0.001, n = 78) or both (16.5 +/- 3.0 mmHg, p less than 0.001, n = 19). Portal pressure was similar in patients bleeding from varices and erosive gastritis (16.7 +/- 3.4 mmHg, n = 43; vs 16.2 +/- 4.0 mmHg, n = 6, respectively) and in patients with refractory and nonrefractory ascites (16.2 +/- 3.5, n = 21; vs 16.2 +/- 3.5 mmHg, n = 57). The lowest portal pressure recorded in a patient with variceal bleeding was 9.0 mmHg. The lowest portal pressure recorded in a patient with ascites was 8.0 mmHg. Esophageal varices (graded 0-4 at endoscopy) were larger in patients with a history of bleeding from esophageal varices as compared to patients without such a history (3.2 +/- 0.7 vs 2.0 +/- 0.9, p less than 0.001). Serum albumin concentration was greater in patients without ascites as compared to patients with ascites (33 +/- 5 vs 26 +/- 5 g/l p less than 0.001) but was similar in patients with refractory and nonrefractory ascites (25 +/- 7 vs 26 +/- 5 g/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Variceal and other portal hypertension related bleeding

Variceal bleeding is one of the commonest and most severe complications of liver cirrhosis. Even with the current best medical care, mortality from variceal bleeding is still around 20%. When cirrhosis is diagnosed, varices are present in about 30–40% of compensated patients and in 60% of those who present with ascites. Once varices have been diagnosed, the overall incidence of variceal bleeding is in the order of 25% at two years. Variceal size is the most useful predictor for variceal bleeding, other predictors are severity of liver dysfunction (Child–Pugh classification) and the presence of red wale marks on the variceal wall. The current consensus is that every cirrhotic patient should be endoscopically screened for varices at the time of diagnosis to detect those requiring prophylactic treatment. Non-selective beta-adrenergic blockers (NSBB) and endoscopic band ligation (EBL) have been shown effective in the prevention of first variceal bleeding. The current recommendation for treating acute variceal bleeding is to start vasoactive drug therapy early (ideally during the transferral or to arrival to hospital, even if active bleeding is only suspected) and performing EBL. Once bleeding is controlled, combination therapy with NSBB + EBL should be used to prevent rebleeding. In patients at high risk of treatment failure despite of using this approach, an early covered-TIPS within 72 h (ideally 24 h) should be considered. Data on management of gastric variceal bleeding is limited. No clear recommendation for primary prophylaxis can be done. In acute cardiofundal variceal bleeding, vasoactive agents together with cyanoacrylate (CA) injection seem to be the treatment of choice. Further CA injections and/or NSBB may be used to prevent rebleeding. TIPS or Balloon-occluded retrograde transvenous obliteration when TIPS is contraindicated may be used as a rescue therapy.