Sex and test verification bias. Impact on the diagnostic value of exercise echocardiography

This trial represents the Egyptian experience in cyanoacrylate injection for hemostasis of bleeding gastric varices. One hundred patients with portal hypertension due to schistosomal hepatic fibrosis and/or posthepatitic liver cirrhosis were included. All patients presented with bleeding from gastric varices either fundal (80 patients) or inferior extension of esophageal varices (20 patients) were enrolled. Injection therapy was administered as the first active measure. No tamponade or drugs were used. Cyanoacrylate was mixed with lipid and injected through a hand-made probe. A mean of 3 (range 1-9) ampoules of cyanoacrylate were used per injection session. Bleeding stopped at the end of all sessions. Ten patients (12.5%) with fundal varices had rebleeding during the first 24 hours. Reinjection could control bleeding in 6 patients with a total success rate of 95%. Four patients were managed surgically. Fatal pulmonary embolism developed in one patient (1.25%) with fundal varix. Five more patients (6.25%) died from bleeding-related liver failure. In conclusion, injection of cyanoacrylate is highly satisfactory in controlling bleeding from both types of gastric varices.     

Recurrent source of bleeding in patients with esophageal varices]

During last 7 years were in Endoscopic Centre of Brno Traumatologic Hospital treated 824 patients (624 male, 200 female) with esophageal varices, indicated to endoscopic sclerotherapy, ligation, or tissue adhesive injection. For one or more episodes of bleeding were treated 659 patients and resting 165 received therapy prophylactically. Recurrent acute bleeding from upper GIT occurred from 1 January 1990 to 30 April 1997 in 212 of them. In patients with previously proved esophageal varices were investigated for repetitive acute bleeding in this period 212 of them. In 157 (74%) patients endoscopy confirmed expected repetitive bleeding from esophageal varices, but in 55 (26%) was found bleeding from other source of upper gastrointestinal tract. The bleeding from gastroduodenal ulcers in 18 (8%) patients, in 22 (10%) from apths, Mallory-Weiss syndrome was source of bleeding in 8 (4%) patients, and hemorrhagic gastropathy in 7 (3%) was found. The authors draw attention to the fact that, in their big group patients with esophageal varices, duplicity of source of bleeding occurred in 1/4 patients. They concluded, that in patients with previously proved esophageal varices in necessary to perform in case of recurrent bleeding emergency of urgent endoscopy not only of esophagus, but even of whole upper GIT. Therapeutic mistake can happen in 1/4 of patients, if repetitive bleeding from varices would be expected and automatically treated by balloon tube. The patients could be damaged by delay in the treatment of bleeding from other source.     

Longer treatment with vasoactive drugs to prevent early variceal rebleeding in cirrhosis

Bleeding oesophageal varices (BOV), resulting from portal hypertension, can prove fatal. Not only is it important to stop the initial bleeding, which may lead to hypovolaemic shock, but also to treat this condition in the longer term, and, consequently, the prevention of rebleeding needs to be addressed. This review highlights the current findings on the haemostatic drug, terlipressin, focusing particular attention on the potential for longer-term treatment strategies in the prevention of rebleeding. The efficacy of terlipressin in treating acute BOV, its low incidence of severe side-effects (comparable to those of somatostatin) and its favourable comparison with sclerotherapy in the prevention of early rebleeds, all indicate the potential for terlipressin administration to be extended to 5 days in the longer-term treatment of BOV. In addition, terlipressin administration, in conjunction with sclerotherapy, can significantly reduce the likelihood of rebleeding compared with sclerotherapy alone and further supports its potential use in the longer-term treatment of BOV.     

The immunomodulatory compound 2-acetyl-4-tetrahydroxybutyl imidazole causes sequestration of lymphocytes in non-lymphoid tissues

Variceal bleeding is the second cause of death in cirrhosis. To achieve haemostasis, sclerotherapy (or banding) is the first line treatment but vasoactive drugs (terlipressin or somatostatin) are an alternative and even a complement. Porto-systemic shunt is to be rapidly considered if a second endoscopic treatment has failed. Primary prevention lies on beta-blockers (propranolol or nadolol). Organic nitrates are an alternative and even a complement. Secondary prevention lies on banding or sclerotherapy; beta-blockers are an alternative and even a complement.     

Maternal respiratory arrests, severe hypotension, and fetal distress after administration of intrathecal, sufentanil, and bupivacaine after intravenous fentanyl

The transjugular intrahepatic portosystemic shunt procedure is an effective intervention for patients with bleeding esophageal varices. Potential complications are numerous but rarely serious. A case of hemopericardium, cardiac tamponade, and death caused by perforation of the right atrium and aorta by a stent after embolization from the liver during stent placement is reported.     

The Saeed Six-Shooter: a prospective study of a new endoscopic multiple rubber-band ligator for the treatment of varices

BACKGROUND AND STUDY AIMS: Rubber-band ligation is superior to sclerotherapy, and is considered to be the endoscopic treatment of choice for bleeding varices. The single-shot mechanism of the ligation device generally used is inherently inefficient, and makes the procedure tedious. It also requires overtube placement, associated with discomfort and complications. This study describes the Saeed Six-Shooter, a multiple ligation device. PATIENTS AND METHODS: Twenty-seven consecutive patients with variceal bleeding were prospectively studied. After initial endoscopic ligation, subsequent sessions were every 7-10 days. The parameters studied were the ease of use, the ability to control active bleeding and eradicate varices, survival, and complications. RESULTS: Active bleeding was controlled in all seven (100%) patients. Esophageal varices were eradicated in 70% (3.2 +/- 1.2 sessions), and gastric varices in 88% of patients (2 +/- 1.2 sessions). Five patients re-bled, two from esophageal varices, two from gastric varices, and one from treatment-induced ulcer. There were four deaths, none due to exsanguination. A single complication, esophageal stricture, resolved with balloon dilation. Intubation was no more difficult with the endoscope loaded with the Six-Shooter than with the endoscope alone (P > 0.3). Six ligations were performed in 39% of cases within 60 seconds, and in 74% of cases within 90 seconds. For gastric varices, the device was effectively used with the endoscope retroflexed. CONCLUSIONS: The Saeed Six-Shooter is a safe and efficient instrument for the endoscopic ligation of varices, and has overcome the limitations of the single-shot ligator.     

Prophylactic endoscopic sclerosing treatment of the esophageal wall in varices -- a prospective controlled randomized trial

From January 1, 1978 to January 1, 1980 a controlled randomized trial comparing conservative treatment with prophylactic sclerotherapy of esophageal varices prior to hemorrhage was carried out. In all 71 patients liver cirrhosis was histologically confirmed. The two randomly assigned groups were comparable. Indications of endoscopic treatment were the existence of varices III-IV bearing erosions, varices II-IV without erosions but coagulation factors below 30%, or both. Six patients left the trial. In group Ia -- treatment by conservative means -- a high rate of variceal bleeding and death was observed. Comparing these results with those of group Ib treated by sclerotherapy, bleeding and death rates were found to be highly significantly lower. -- Thus the investigated criteria for predicting a recent variceal hemorrhage are confirmed. Prophylactic sclerotherapy in esophageal varices with erosions and/or poor coagulation reserve of the liver can largely prevent an esophageal hemorrhage from varices, and prolongs the life of these chronically ill patients.     

Endoscopic variceal ligation in prophylaxis of first variceal bleeding in cirrhotic patients with high-risk esophageal varices

To determine the efficacy of endoscopic variceal ligation (EVL) in prophylaxis on the rate of first esophageal variceal bleeding, we conducted a prospective, randomized trial in 126 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. Life-table curves showed that prophylactic EVL significantly diminished the rate of variceal hemorrhage (12/62 [19%] vs. 38/64 [60%]; P = .0001) and overall mortality (17/62 [28%] vs. 37/64 [58%]; P = .0011). The 2-year cumulative bleeding rate was 19% (12/ 62) in the EVL group and 60% (38/64) in the control group. The 2-year cumulative mortality rate was 28% (17/62) in the EVL group and 58% (37/64) in the control group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed significantly lower mortality in the ligation group (P = .001). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. The lower risk in the EVL group was attributed to a rapid reduction of variceal size. Prophylactic EVL was more efficient in preventing first bleeding in patients with good condition (Child A) than in those with decompensated disease (Child B and C). We conclude that prophylactic EVL can decrease the incidence of first variceal bleeding and death over a period of 2 years in cirrhotic patients with high-risk esophageal varices.     

Histotopographic distribution of placental inflammation: analysis of 22 cases

OBJECTIVES: Acute bleeding from esophageal varices is a major complication of cirrhosis. Despite the large number of published studies no predictive factors of control of bleeding have been identified. We assessed the clinical and biological factors predictive of bleeding control within the first 2 weeks after a bleeding episode in a homogeneous group of patients enrolled in a large multicenter trial, who underwent a standardized emergency sclerotherapy session. METHODS: 101 patients with cirrhosis were enrolled. All had endoscopy-proven variceal bleeding, and the interval between hematemesis or melena and emergency sclerotherapy was always less than 24 hours. A second sclerotherapy session and other methods for the prevention of rebleeding were allowed after 5 days. RESULTS: Treatment failed in 16 patients after 24 hours and in a total of 33 patients after 15 days. Three of the 17 variables included in multivariate logistic analysis were associated with failure at 24 hours: encephalopathy (P = 0.006, OR = 4.0), blood transfusion prior to sclerotherapy (P = 0.012, OR = 6.2) and previous propranolol therapy (P = 0.022, OR = 4.6). Two variables were associated with failure between 24 hours and day 15 in patients successfully controlled after 24 hours: an interval between the onset of bleeding and sclerotherapy of less than 12 hours (P = 0.010) and blood transfusion (P = 0.018). After 15 days, three variables were associated with failure in a multivariate Cox model: encephalopathy (P = 0.0025, OR = 2.3), time to sclerotherapy (P = 0.022, OR 2.3) and blood transfusion before sclerotherapy (P = 0.0005, OR = 4.0). CONCLUSION: Encephalopathy, the severity of bleeding, assessed in terms of transfusion requirements, and the time between clinically overt bleeding and sclerotherapy are the main predictive factors of failure of the control of bleeding after emergency sclerotherapy for acute bleeding from esophageal varices.     

Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial

This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding.     

Effect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis

BACKGROUND/AIMS: Cirrhosis with portal hypertension is associated with changes in the splanchnic and systemic haemodynamics, and subsequent complications, such as bleeding from oesophageal varices, have led to the introduction of long-acting somatostatin analogues in the treatment of portal hypertension. However, reports on the splanchnic and systemic effects of octreotide are contradictory and therefore the aim of the present study was to assess the effects of continuous infusion of octreotide on central and systemic haemodynamics, portal pressures, and hepatic blood flow. METHODS: Thirteen patients with cirrhosis underwent liver vein catheterisation. Portal and arterial blood pressures were determined at baseline and 10, 30, and 50 min after a bolus injection of octreotide 100 micrograms, followed by continuous infusion of octreotide 100 micrograms/ h for 1 h. Hepatic blood flow, cardiac output, central and arterial blood volume, and central circulation time were determined at baseline and 50 min after the start of the octreotide infusion. RESULTS: The mean arterial blood pressure increased during the first 10 min (p < 0.0005), but returned to baseline after 50 min. The central and arterial blood volume (-16%, p < 0.005) and the central circulation time (-8%, p < 0.05) were significantly decreased after 50 min, whereas the cardiac output did not change significantly. The hepatic venous pressure gradient and the hepatic blood flow did not change significantly at any time after infusion of octreotide. CONCLUSIONS: Octreotide does not affect the portal pressure or hepatic blood flow, whereas it may further contract the central blood volume and thereby exert a potentially harmful effect on central hypovolaemia in patients with cirrhosis. However, these early effects do not exclude the possibility that administration of longacting somatostatin analogues over a longer period may have a beneficial effect.     

A prospective randomized trial comparing somatostatin and sclerotherapy in the treatment of acute variceal bleeding

Somatostatin and endoscopic sclerotherapy are widely used in the treatment of acute variceal bleeding. Although objective evidence does exist about the advantages of either treatment, data comparing both procedures are scarce. In order to compare the effectiveness and safety of somatostatin and sclerotherapy in the treatment of acute variceal bleeding, 70 consecutive cirrhotic patients suffering from esophageal variceal hemorrhage and meeting the inclusion criteria were randomly assigned to treatment with somatostatin (35 patients) or sclerotherapy (35 patients). No differences in age, sex, alcohol intake, etiology of cirrhosis and severity of liver failure were found between groups. Failure of treatment (defined as persistence of bleeding despite therapy or subsequent rebleeding within the 48-hr trial period) occurred in seven patients (20%) in the somatostatin group and in six (17.1%) in the sclerotherapy group (NS). Early rebleeding occurred in seven of 28 patients (25%) in the somatostatin group and in five of 29 (17.2%) in the sclerotherapy group (NS). Mortality within the first 6 wk was no different between both groups: 10 (28.5%) and eight (22.8%) in the somatostatin and sclerotherapy groups, respectively. Sclerotherapy, but not somatostatin, was associated with major complications in five cases (14.2%) (p = 0.026), two of which resulted in patient's death. These results suggest that somatostatin is safer, and as effective as sclerotherapy, in controlling acute variceal bleeding until an elective treatment can be established.     

Endoscopic ligation with elastic bands in the prevention of hemorrhage recurrence caused by esophageal varices. Study of 45 patients

The aim of the present study was to determine the usefulness of elastic band ligation in the prevention of hemorrhage recurrence by esophageal varices. Forty-five patients without known hepatocarcinoma who had survived a hemorrhagic variceal episode were included in the study. Seventeen patients (38%) were Child-Pugh A, 22 (49%) B, and 6 (13%) C, with the hepatitis C virus and alcohol being the etiology of cirrosis in 55 and 20% of the cases, respectively. The first ligation session was performed between the third and fifth days after the hemorrhagic episode and the posterior sessions were carried out at intervals of 2-4 weeks. The ligation sessions were performed without antibiotic prophylaxis and with placement of an overtube. A mean of 4 +/- 2 bands were placed per session (range, 1-8) and the mean number of sessions required per patient to achieve erradication of the varices was 3.5 +/- 1.5 (range, 2-8). The rate of bleeding recurrence was 17.7% (9 episodes, five by variceal rupture and four by ulcer secondary to ligation). All the episodes of bleeding recurrence occurred between the sessions, with the mortality being 11% (5/45 patients). In the 40 remaining patients the varices were erradicated although 19 (47.5%) required one or two additional sessions of sclerotherapy. The accumulated percentage of patients free of bleeding recurrence was 82% during a mean follow-up of 10.2 +/- 6.7 months. Ten lesions of dislaceration of the esophageal mucosa caused by placement of the were observed overtube. In conclusion, endoscopic elastic band ligation is a useful technique for the erradication of esophageal varices an in the prevention of bleeding recurrence.     

Jejunal variceal bleeding after esophageal transection in a patient with idiopathic portal hypertension

This report describes a 38-year-old man with massive gastrointestinal bleeding from jejunal varices. He had been previously diagnosed to have idiopathic portal hypertension and esophageal varices, and had undergone an esophageal transection 8 years earlier. The pre-operative diagnosis was a suspected hemorrhage from the small intestine as visualized by 99mTc-HSAD scintigraphy (technetium 99m-labeled human serum albumin D-type) and was not considered to be repeated massive lower GI tract bleeding. An exploratory laparotomy was performed, and intra-operative endoscopy revealed active bleeding from the jejunal varices. A partial resection of the small intestine resulted in a complete resolution of the bleeding. A review of the literature thereafter disclosed twelve previously reported cases of jejunal variceal bleeding.     

Management of esophageal varices in children by endoscopic variceal ligation

Endoscopic variceal sclerotherapy (EVS) has been considered the mainstay of therapy for bleeding esophageal varices in adults. However, recent data have shown that endoscopic variceal ligation (EVL) is just as efficacious and has fewer complications than EVS. Although there are many reports concerning EVL in adults, only a few studies have been done in children. This report describes experience with EVL in 22 children with esophageal variceal hemorrhage. Eighty-seven EVL procedures were performed during a 9-year period in 22 children. The causes of portal hypertension were biliary atresia (10), portal vein thrombosis (8), chronic active hepatitis (1), cirrhosis secondary to cystic fibrosis (2), and primary sclerosing cholangitis (1). The age range at the onset of variceal bleeding was 8 months to 19 years. Twelve patients had EVS before EVL treatment was begun. Distal esophageal varices (one to four per session) were mechanically ligated using an elastic band ligature device attached to a flexible endoscope. The aim of therapy was obliteration of distal esophageal varices by EVL, every 2 to 4 weeks, until eradication. Subsequent EVL was dictated by the status of the varices. Outcome was assessed with respect to survival, rebleeding, status of varices, and complications. The patients underwent a mean of four sessions of EVL (range, one to eight). Four patients subsequently underwent liver transplantation. Of the 18 patients remaining (average follow-up period, 5.3 years), 12 had their varices eradicated (average of four EVL sessions), four are still in treatment, one has not been evaluated in the past 4 years, and one died of liver failure. Complications included bleeding between sessions (6 patients), cervical esophageal perforation (1 patient), and transient fever (2 patients). No child has experienced symptoms of esophageal stenosis or gastroesophageal reflux. Two patients died of liver disease, unrelated to bleeding from portal hypertension. EVL is effective in controlling variceal hemorrhage in children with portal hypertension, regardless of etiology. The complication rate is low, and EVL is an acceptable and perhaps preferable alternative to EVS in children with esophageal varices.     

Transthoraco-phrenic esophageal transection with paraesophago-gastric devascularization and splenectomy using a stapler

BACKGROUND/AIMS: Surgery remains the most reliable treatment for bleeding esophageal varices. The aim of this study was to introduce the operative technique of transthoraco-phrenic esophageal transection with paraesophagogastric devascularization using a stapler and to evaluate surgical results. METHODS: Forty-five patients underwent the procedure; an elective procedure was performed in 22 patients (bleeders) and a prophylactic procedure in 23 patients (nonbleeders). Twenty-nine patients were classified as Child's A, 15 as B and 1 as C. Previous sclerotherapy had been performed in 5 patients. RESULTS: No hospital deaths occurred. No patients developed postoperative anastomotic leakage, encephalopathy, or any complications related to phrenicotomy. Three patients bled postoperatively from recurrent esophageal varices. Cumulative 5-year bleeding rates were 5.0% in bleeders and 6.6% in non-bleeders. Two patients died due to bleeding varices. Cumulative 5-year survival rates were 72.1% and 78.8% in patients classified as Child's A and Child's B, respectively. CONCLUSIONS: This procedure may be indicated for a majority of Child's A or B patients. Although the advantages of this procedure must be evaluated further, it may be an alternative when injection sclerotherapy and endoscopic ligation fail.     

The identification of high risk knee bleeds in adolescents with severe haemophilia A

One hundred and thirty-seven knee bleeds treated with an initial dose of 11-16 units of factor VIII/kg have been reviewed in an attempt to find the predictive factors for bleeds requiring retransfusion. Thirty-two bleeds (23.4%) were retransfused within 48 hours because of extension of bleeding or poor progress. Fifty-nine per cent of bleeds which were retransfused presented with pain and 72% were tender at presentation. These figures contrasted with those for bleeds which were not retransfused of 30% and 45%. The difference in each case is significant. Forty-seven per cent of retransfused bleeds presented with less than 50% of normal movement against 12% who were not retransfused. This difference was also highly significant. It is suggested that knee bleeds presenting with pain, tenderness and/or more than 50% restriction of movement should be considered for higher initial doses of factor VIII.     

Coagulation studies and platelet function after somatostatin infusion

The effect of short- and long-term somatostatin (GIF) administration on haemostatic function in man was investigated. The dosage programme applied in this study was 250 mug GIF as a bolus injection and 250 mug GIF/h by way of infusion. In five healthy volunteers a short-term (3h) treatment resulted in a statistically significant drop of platelet count and impairment of platelet aggregation at the end of infusion. However, these changes were within the physiologically normal range and disappeared after two hours on all subjects. Other parameters such as bleeding time, thromboplastin and partial thromboplastin time, fibrinogen, fibrin/fibrinogen split products, plasma factor XIII, ethanol gelation test were not affected. In two patients with gastric haemorrhage and persistent amylasaemia a 67 or 120-h treatment induced no remarkable haemostatic defect. By contrast, peptic ulcer bleeding in one patient stopped 60 min after starting the GIF infusion. These studies indicated that somatostatin administration in man at the dosage programme used neither results in clinical evidence indicating bleeding tendency nor does it influence laboratory parameters in an apparent way.     

The postprandial portal flow is related to the severity of portal hypertension and liver cirrhosis

BACKGROUND/AIMS: Diminished postprandial portal hyperemia has been demonstrated by echo-Doppler flowmetry in patients with liver cirrhosis, but its diagnostic role is unclear. This prospective study was therefore undertaken in patients with varying severity of portal hypertension and degree of liver cirrhosis. METHODS: Portal flowmetry was performed in 66 patients with cirrhosis and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Hemodynamic parameters were related to the degree of esophageal varices, variceal bleeding, portal hypertensive gastropathy and Child-Pugh score. RESULTS: The postprandial portal blood velocity increment was low in patients with esophageal varices of any degree (22-24%), compared to patients without varices (49%, p<0.01) and healthy controls (65%, p<0.001), but was not different in patients with or without variceal bleeding (22% vs. 20%). In contrast, the congestion index (CI; ratio of portal vein cross-sectional area and portal blood velocity) pre-/postprandial decreased in the bleeding group only (CI pre/ CI post 1.30+/-0.23 (no bleeding) vs. 0.86+/-0.29 (bleeding); p<0.01). Portal hypertensive gastropathy was not related to any of the portal flow parameters. The portal blood velocity increment was comparable in controls (65%) and patients with Child-Pugh class A cirrhosis (56%), but lower in patients with class B (32%) and class C cirrhosis (15%, p<0.05 vs. class A). Also, there was no postprandial decrease in congestion index in patients with the most severe cirrhosis (p<0.01 class C vs. class A and B). CONCLUSIONS: The postprandial rise in portal flow is inversely related to the severity of portal hypertension and liver cirrhosis, and may be a valuable parameter with respect to the risk of variceal bleeding.     

Chronic liver failure induced by long-term administration of tegafur: a case report

A 55 year-old man was admitted with massive ascites. Although the laboratory data on admission were compatible with hepatic cirrhosis and remarkable esophageal varices were observed during endoscopy, the imaging findings such as computed tomography and ultrasonographic examination did not confirm hepatic cirrhosis. The patient had no history of alcohol abuse, blood transfusions or acute hepatitis. Serological markers related to viral and autoimmune hepatitis were all negative. Seven years ago, the patient had undergone an operation for colon cancer and has been taking tegafur since then for a total of 55 months. Tegafur was suspected as the causative agent for the liver dysfunction of this patient and the administration of tegafur was stopped. His laboratory data improved gradually and the ascites vanished. The first liver biopsy performed 6 months after discontinuation of tegafur still revealed chronic active hepatitis. However, at the liver biopsy performed 18 months after withdrawal of tegafur, inflammatory activity had subsided and the third liver biopsy, performed 34 months thereafter, revealed further improvement of the pathological changes that had occurred in the liver. We therefore conclude that the administration of tegafur may have caused chronic active liver injury with portal hypertension manifested as ascites and esophageal varices.