Esophageal Variceal Bleeding Episodes Research Articles

Secondary Prevention of Esophageal Variceal Bleeding Is Often Imperfect: A National, Population-Based Cohort Study of 3592 Patients

Secondary prevention of esophageal variceal bleeding is important to improve prognosis, but uptake of guidelines is unknown in a real-world setting. Here, we determined the proportion of patients receiving appropriate nonselective beta-blocker treatment and repeat upper endoscopy after a first episode of esophageal variceal bleeding within a reasonable time frame. Population-based registers were used to identify all patients with a first episode of esophageal variceal bleeding in Sweden from 2006 to 2020. Crosslinkage between registers was performed to receive information on the cumulative incidence of patients with a dispensation of nonselective beta-blockers and repeat upper endoscopy within 120 days from baseline. Overall mortality was investigated using Cox regression. In total, 3592 patients were identified, with a median age of 63 (interquartile range, 54-71) years. The cumulative incidence of a dispensation of nonselective beta-blockers and a repeat endoscopy within 120 days was 33%. A total of 77% received either of these treatments. Overall mortality was high, with 65% of patients dying after esophageal variceal bleeding during the full follow-up period (median 1.7 years). We observed an improved overall mortality during the later years of the study period (adjusted hazard ratio for the 2016-2020 period compared with the 2006-2010 period, 0.80; 95% confidence interval, 0.71-0.89). Patients with receipt of nonselective beta-blockers and repeat upper endoscopy had better overall survival compared with those without (adjusted hazard ratio, 0.80; 95% confidence interval, 0.72-0.90). Secondary prevention of esophageal variceal bleeding has not been widely undertaken, with many patients not receiving guideline-supported interventions within a reasonable time frame. This highlights a need to raise awareness on appropriate prevention strategies to clinicians and patients.

Balloon-compression endoscopic injection sclerotherapy versus transjugular intrahepatic portosystemic shunt for esophageal variceal rebleeding.

In cirrhotic patients, recurrent bleeding after the first episode of esophageal variceal bleeding (EVB) is common and lethal. The present study was aimed to compare balloon-compression endoscopic injection sclerotherapy (bc-EIS) with transjugular intrahepatic portosystemic shunt (TIPS) for the prophylaxis of variceal rebleeding. Between June 2020 and September 2022, 81 cirrhotic patients with EVB (42 in the bc-EIS group and 39 in the TIPS group) were evaluated retrospectively. The occurrence of rebleeding, hepatic encephalopathy (HE) or other complications, as well as liver functions and survival rate were compared between two groups. During the 12months of follow-up, variceal eradication was achieved in 40 (95.24%) patients of the bc-EIS group after a mean of 1.80 ± 0.94 sessions. TIPS was successfully performed in 39 (100%) patients. No significant difference in the variceal rebleeding rate was observed between bc-EIS and TIPS groups (16.67vs. 17.95%; p = 0.111). While the bc-EIS group showed significantly decreased incidence of HE (2.38 vs. 17.95%;p < 0.001) and lower level of total bilirubin (p < 0.05) in comparison with the TIPS group. The difference in mortality between the two groups failed to reach statistical significance (0.00 vs. 7.69%; p = 0.107). Bc-EIS is not inferior to TIPS in the survival and control of variceal rebleeding, but associated with decreased risk of HE and liver dysfunction.

Influence of esophageal flap valve on esophageal variceal bleeding

Background and Aim: Increased exposure to gastric acid in patients with abnormal gastroesophageal flap valve (GEFV) may lead to increase esophageal variceal bleeding. We aimed to investigate the relationship between GEFV and esophageal variceal bleeding episodes. Methods: It is an interim analysis of a cross-sectional study involving 109 patients with esophageal varices and flap valve of any grade. Patients are divided into two groups on basis of Hill’s grade of flap valve (Hill’s grade 1,2-normal and Hill’s grade 3,4-abnormal). They are assessed with esophagogastroduodenoscopy and incidence of variceal bleeding and size of varices (Two groups: large{>5mm} and small {<5 mm} varices) are compared with Hill’s Grade of flap valve. Results: This study included 109 patients out of which 72 had normal and 37 had abnormal flap valve. Number of bleeding episodes was significantly higher in patients with esophageal varices who had abnormal flap valve compared to whom having normal flap valve (Mean number of bleeding episodes- 2.5 vs 1.1, p<0.001). Predominantly, patients with abnormal flap valve had larger varices while patients with normal flap valve had smaller varices (94.6% vs 73.6%, p<0.001). Conclusions: Abnormal GEFV is independent risk factor for esophageal variceal bleeding.

Lower 90-day Hospital Readmission Rates for Esophageal Variceal Bleeding After TIPS: A Nationwide Linked Analysis.

Hospital readmission rates following a transjugular intrahepatic portosystemic shunt (TIPS) insertion after an episode of esophageal variceal bleeding (EVB) has not been well studied. We aimed to address this gap in knowledge on a population level. The Nationwide Readmission Database (NRD) was used to study the readmission rates for patients with decompensated cirrhosis who had a TIPS insertion performed for EVB. The NRD is a national database that tracks patients longitudinally for hospital readmissions. A propensity score matching model was created to match patients who received TIPS with those who did not. A total of 42,679,001 hospital admissions from the 2012 to 2014 NRD sample were analyzed. There were 33,934 patients with EVB who met inclusion criteria for the study, of whom, 1527 (4.5%) received TIPS after EVB and were matched with 1527 patients with EVB who did not undergo TIPS. With a uniform follow-up of 3 months, patients with TIPS were less likely to be readmitted to hospital with a recurrent EVB [odds ratio (OR): 0.33, 95% confidence interval (CI): 0.24-0.47, P<0.01], although were more likely to be readmitted with hepatic encephalopathy (OR: 1.66; 95% CI: 1.31-2.11, P<0.01). At 3 months, there was no difference in all cause hospital readmission rate between the 2 groups (OR: 38.8%; 95% CI: 38.1-44.9 TIPS vs. OR: 41.5%; 95% CI: 34.1-43.3 non-TIPS: P=0.17). In this large nationally representative study, TIPS insertion after an episode of EVB was associated with a significantly lower risk of 3-month readmission for recurrent EVB compared with patients who did not receive TIPS. Although those receiving TIPS had a higher rate of hepatic encephalopathy the overall readmission remained unchanged.

Results of treatment of esophageal variceal hemorrhage with endoscopic injection of n-butyl-2-cyanoacrylate in patients with Child-Pugh class C cirrhosis.

Background and study aims: The results of endoscopic treatment with elastic band ligation for esophageal variceal bleeding in patients with Child-Pugh class C cirrhosis remain poor. In comparison with treatment with elastic band ligation, we have found lower rates of rebleeding and mortality with n-butyl-2-cyanoacrylate injections. Thus, the aim of the current study was to describe our unit’s 10 years of experience with injection of n-butyl-2-cyanoacrylate to control esophageal variceal ruptures in patients with Child-Pugh class C cirrhosis. Patients and methods: A single-center, retrospective study was conducted. Sixty-three patients with Child-Pugh class C cirrhosis had been admitted to the center with an acute episode of esophageal variceal bleeding. All were treated with injection of n-butyl-2-cyanoacrylate. The patients were assigned to 1 of 2 groups according to their Child-Pugh class C cirrhosis scores: group I (score range, 10 through 13 points) and group II (score, 14 or 15 points). The 3 variables studied were rates of initial failure to control bleeding, failure to prevent rebleeding (secondary prophylaxis), and mortality. Patients in the 2 groups (group I, n = 50; group II, n = 13) had similar characteristics. Results: Bleeding was successfully controlled in almost 75 % of the patients during the first 5 days after treatment, with no significant differences observed between groups I and II. There were no significant differences between the 2 groups with respect to mortality rate for the first 5 days after treatment. Thirty-four patients (54 %) were free of bleeding at 6 weeks after treatment, with a significant difference noted between the groups: group I, 64 %, versus group II, 15.4 % (P < 0.001). The overall mortality rate was 44.4 %, with a significant difference noted between the groups: group I, 34 %, versus group II, 84.6 % (P < 0.001). Conclusion: Endoscopic injection of n-butyl-2-cyanoacrylate is a valid treatment option to control esophageal variceal bleeding in patients with a Child-Pugh class C cirrhosis score in the range of 10 through 13 points.

T1006 Poor Adherence to Guidelines for Prevention of Recurrent Variceal Bleeding Among Veterans

Background: Variceal hemorrhage is the most lethal complication of cirrhosis, with 20% mortality rate within the first 6 weeks. When untreated, the risk of rebleeding is as high as 60% within 2 years. Guidelines have been proposed by the AASLD to prevent recurrence of variceal hemorrhage. We hypothesize that adherence to these guidelines is suboptimal at this Veterans Affairs Hospital. Aims: (1) To determine the proportion of patients who adhered to current AASLD guidelines for secondary prophylaxis of variceal bleeding, (2) to identify barriers to adherence and (3) to compare outcomes between patients who were compliant and those non-compliant with the guidelines. Methods: All cirrhotic patients presenting to the NF/SGVHS with an index episode of esophageal variceal bleeding between 1/1/2000 and 12/31/ 2008 were identified. Individual charts were reviewed. Primary endpoints were rebleeding or death. Statistical analyzes were performed as appropriate. Results: 67 male patients were included, mean age 59 years old (range 35-81), and followed for a mean of 18.7 months (range 0-85). Beta-blockers were initiated prior to discharge in 55 patients (82%). After index EVL, GI recommended repeat EGD in 46/67 (69%), EGD was ordered prior to discharge in 37/67 (55%), and performed within the guideline recommended 7-14 days in only 4/67 (6%). 18/67 (27%) had EVL within 30 days. Reasons for nonadherence were: MD did not order EGD in 16/32 (50%), patient cancelled in 13/32 (41%) and clinic cancelled in 3/32 (9%). Regardless of the interval between EGDs, 26 patients achieved eradication of varices, and only 9 (13.4%) had follow-up EGD for confirmation of eradication. In all, 26 patients (38.8%) suffered a rebleeding episode, and 51 (76%) were deceased by the end of the study period. Rebleeding rate was 25% of those re-scoped within 2 weeks, 35.7% of those re-scoped within 15-30 days, and 40% of the remaining patients (p=NS). There was also no difference in rebleeding rate according to eradication status. However, mortality was higher among patients who did not achieve eradication (55% vs. 21%, p= 0.0011). Conclusion: Only a negligible proportion of patients undergo appropriate secondary prophylaxis for esophageal variceal bleeding and this poor adherence is associated with increased mortality. Further efforts should be directed toward strategies to provide guideline concordant care should be targeted towards educating providers and identifying patient centered barriers to adherence. One strategy we are exploring is the creation of an order set for EGD scheduling prior to discharge.

T1007 Survey of Current Opinions and Practices in Hepatitis C

Background: Variceal hemorrhage is the most lethal complication of cirrhosis, with 20% mortality rate within the first 6 weeks. When untreated, the risk of rebleeding is as high as 60% within 2 years. Guidelines have been proposed by the AASLD to prevent recurrence of variceal hemorrhage. We hypothesize that adherence to these guidelines is suboptimal at this Veterans Affairs Hospital. Aims: (1) To determine the proportion of patients who adhered to current AASLD guidelines for secondary prophylaxis of variceal bleeding, (2) to identify barriers to adherence and (3) to compare outcomes between patients who were compliant and those non-compliant with the guidelines. Methods: All cirrhotic patients presenting to the NF/SGVHS with an index episode of esophageal variceal bleeding between 1/1/2000 and 12/31/ 2008 were identified. Individual charts were reviewed. Primary endpoints were rebleeding or death. Statistical analyzes were performed as appropriate. Results: 67 male patients were included, mean age 59 years old (range 35-81), and followed for a mean of 18.7 months (range 0-85). Beta-blockers were initiated prior to discharge in 55 patients (82%). After index EVL, GI recommended repeat EGD in 46/67 (69%), EGD was ordered prior to discharge in 37/67 (55%), and performed within the guideline recommended 7-14 days in only 4/67 (6%). 18/67 (27%) had EVL within 30 days. Reasons for nonadherence were: MD did not order EGD in 16/32 (50%), patient cancelled in 13/32 (41%) and clinic cancelled in 3/32 (9%). Regardless of the interval between EGDs, 26 patients achieved eradication of varices, and only 9 (13.4%) had follow-up EGD for confirmation of eradication. In all, 26 patients (38.8%) suffered a rebleeding episode, and 51 (76%) were deceased by the end of the study period. Rebleeding rate was 25% of those re-scoped within 2 weeks, 35.7% of those re-scoped within 15-30 days, and 40% of the remaining patients (p=NS). There was also no difference in rebleeding rate according to eradication status. However, mortality was higher among patients who did not achieve eradication (55% vs. 21%, p= 0.0011). Conclusion: Only a negligible proportion of patients undergo appropriate secondary prophylaxis for esophageal variceal bleeding and this poor adherence is associated with increased mortality. Further efforts should be directed toward strategies to provide guideline concordant care should be targeted towards educating providers and identifying patient centered barriers to adherence. One strategy we are exploring is the creation of an order set for EGD scheduling prior to discharge.

Non-cirrhotic extrahepatic portal vein thrombosis: a 6-year long case history

In the absence of liver cirrhosis or cancer, splanchnic vein thrombosis is rare. Additional risk factors are neoplasia, abdominal inflammatory disease, and inherited and acquired thrombophilia as reported in chronic myeloproliferative disorders (CMPD), i.e. polycythemia vera and essential thrombocythemia [1, 2]. The Janus kinase-2 somatic mutation (JAK2V617F) represents a risk factor for myeloproliferative diseases and is helpful in laboratory tests for the evaluation of unexplained abdominal vein thrombosis [3–5]. A 47-year-old man was referred (November 2007) to our gastroenterology unit for further investigations regarding complications related to portal hypertension. Extrahepatic portal vein thrombosis (EHPVT) was diagnosed in another Hospital 6 years before (November 2001) after the onset of acute abdominal pain. Basic investigations were performed in order to diagnose liver cirrhosis as the main cause of splanchnic vein thrombosis. Neither ascites nor encephalopathy was present at the time of EHPVT diagnosis. Computed tomography showed thrombosis of the portal, splenic, and mesenteric veins, without alterations in hepatic pattern. Collateral vessels and portal cavernoma, as well as splenomegaly, were also reported. The patient developed significant portal hypertension with portosystemic collaterals that caused a serious episode of esophageal variceal bleeding in June 2007. Further abdominal ultrasound investigations, confirming the EHPVT, showed a significant enlargement of the spleen (16–17 cm) with signs of portal hypertension. The liver appeared to be slightly enlarged with a normal echo-pattern and regular borders. A splenoportography confirmed the presence of spleno-portal axis thrombosis. Liver biopsy excluded cirrhosis and showed mild portal inflammation with fibrosis confined to portal tracts. In November 2007, when he was referred to our gastroenterology unit, and additional causes of non-cirrhotic EHPVT were investigated (Table 1). Liver routine laboratory examinations did not show any significant alteration. However, despite the considerable splenomegaly (18 cm at abdominal US), platelet count was higher than normal (449 9 10/l). The review of previous clinical and laboratory files showed increased platelet counts ranging from 900 to 449 9 10/l from the first (November 2001) to the last investigation. This feature was never highlighted before our case investigation. We suspected that the normal and sometimes increased platelet count might mask CMPD. A search for the molecular marker, JAK2V617F, was performed by means of PCR assay and was positive in our patient. A bone marrow biopsy showed CMPD with prevalence of megakaryocytes, as well as myelofibrosis, consistent with ‘essential thrombocythemia’. The patient started treatment with acetylsalicylic acid (75 mg/day) and hydroxycarbamide (500 mg/day). Non-cirrhotic EHPVT is quite a rare event [1, 2]. In our patient from the EHPVT onset (6 years before) onwards, despite increasing splenomegaly, platelet counts were observed at the upper level of normal range and sometimes higher than normal. However, they were never investigated until the last admission to our hospital. It could be argued that a myeloproliferative disease was already present at the time of EHPVT diagnosis. Bone marrow biopsy showed an G. Ricci (&) F. Pigo V. Alvisi Department of Clinical and Experimental Medicine, Gastroenterology, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy e-mail: giorgio.ricci@unife.it

Sandostatin causing reversible thrombocytopenia

Esophageal variceal bleeding can be serious or life threatening. Drug-induced thrombocytopenia can further complicate such bleeding episodes. Thrombocytopenia because of sandostatin has been reported in the literature only once previously. We describe a case of sandostatin-induced reversible thrombocytopenia with a positive rechallenge. Platelet count decreased during administration of sandostatin and recovered only when the infusion was halted. The proposed mechanism of thrombocytopenia during both episodes is immunologic. Physician awareness of sandostatin-induced thrombocytopenia can prevent unnecessary complication during episodes of esophageal variceal bleeding and is rapidly reversed with discontinuation of the drug.

Multiple Normal Deliveries in a Woman with Severe Portal Hypertension Due to Congenital Hepatic Fibrosis: The Importance of Preserved Hepatocellular Function

We report a 26-year-old woman with congenital hepatic fibrosis (CHFib), adult polycystic kidney disease, type II diabetes mellitus, and von Willebrand disease, who despite persistent advice to the contrary because of severe portal hypertension, had 5 pregnancies delivering 6 healthy infants over 8 yr. During this time, she experienced several episodes of esophageal variceal bleeding and severe ascites with persistently normal liver and renal function. CHFib is one of the prototypes of portal hypertension with preserved hepatocellular function. Although pregnancy is ill-advised in most women with portal hypertension and particularly with severe manifestations, this report illustrates the importance of preserved hepatocellular function for the outcome of pregnancy in these patients.

Living related liver transplantation for biliary atresia with portopulmonary hypertension: Case report

Portopulmonary hypertension is a complication of end-stage liver disease that adversely affects the outcome of liver transplantation (LT). We report a case of living related LT who developed severe pulmonary hypertension during and after LT. This 16-year-old girl suffered from biliary atresia, having undergone a portoenterostomy at 60 days of age, at the time of discovery of liver cirrhosis. She had been admitted to a local hospital several times for episodes of esophageal variceal bleeding. Neither dyspnea nor cyanosis was discerned until LT. Although pulmonary hypertension (PH) was disclosed by echocardiogram upon preoperative evaluation, we did not consider this a contraindication for LT, because the PH was mild. She underwent living LT from her father (graft volume/recipient body weight ratio: 0.99%). After induction of anesthesia for LT, a pulmonary flotation catheterization showed severe PH (>40 mm Hg). The pulmonary artery pressure continued to be elevated during surgery, although it was possible that her severe scoliosis affected the data. Hyperbilirubinemia was observed after LT, despite good liver function tests. On postoperative day 12, a portal vein thrombosis was detected requiring emergency thrombectomy and splenectomy. Her general condition worsened after the second surgery. She died due to cardiopulmonary failure. Autopsy showed marked hypertrophy of the right ventricle with intimal thickening in the pulmonary artery. In this case, the underestimated PH might have resulted in the unfortunate outcome. Before LT, PH should be carefully evaluated by measures including invasive assessment.

Endoscopic Sclerosis versus Cyanoacrylate Endoscopic Injection for the First Episode of Variceal Bleeding: A Prospective, Controlled, and Randomized Study in Child-Pugh Class C Patients

Despite the recognized efficacy of sclerotherapy and elastic band ligation in controlling variceal hemorrhage, the results of endoscopic treatment in Child-Pugh class C patients remain poor. The aim of this prospective, controlled, and randomized study was to compare conventional sclerotherapy with injection of the tissue adhesive N-butyl-2-cyanoacrylate in controlling the first episode of rupturing of esophageal varices. From January 1994 to June 1997, 36 consecutive Child-Pugh class C cirrhotic patients were admitted with an initial episode of esophageal variceal bleeding. They were randomly assigned to receive sclerotherapy with a 3% ethanolamine oleate solution (group 1, 18 patients) or injection of tissue adhesive (group 2, 18 patients). Episodes of recurrent bleeding were managed after the randomization procedure. After bleeding had been controlled, patients in both groups received weekly sessions of conventional sclerotherapy to eradicate any remaining esophageal veins. The patients in the two treatment groups had similar characteristics on entry into the study. More than 80% of the patients were admitted with moderate or severe hemorrhage. Approximately half of them presented with active bleeding during the index endoscopy. Early recurrent bleeding was observed in ten of the 18 patients in group 1 (55.6%) and in two of the 18 in group 2 (11.1%; P = 0.01). The hospital mortality rates were 72.2% in group I and 33.3% in group II (P = 0.04). These findings support the view that cyanoacrylate injection is superior to conventional sclerosis for controlling esophageal variceal bleeding in Child-Pugh class C patients. It is also highly probable that the better bleeding control achieved using the cyanoacrylate tissue adhesive treatment led to a lower hospital mortality rate.

Prophylactic banding ligation of high-risk esophageal varices in patients with cirrhosis: a prospective, randomized trial

Background/Aims: Injection sclerotherapy has been used to prevent the first episode of variceal hemorrhage, but the results are controversial. The value of banding ligation in the prophylaxis of the first episode of variceal bleeding has not yet been completely evaluated. This study was conducted to determine whether prophylactic banding ligation is beneficial for cirrhotic patients with high-risk esophageal varices. Methods: A total of 127 cirrhotic patients with endoscopically-assessed high-risk esophageal varices but no history of bleeding were randomized to undergo banding ligation (64 patients) or to serve as controls (63 patients). Ligation was performed at 3-week intervals until variceal obliteration was obtained. Results: During a median follow-up of 29 months, 14 patients (21.8%) in the ligation group and 22 patients (34.9%) in the control group experienced upper gastrointestinal bleeding ( p=0.15). Variceal bleeding occurred in eight patients (12.5%) in the ligation group and 14 patients (22.2%) in the control group ( p=0.22). Blood transfusion requirements were fewer in the EVL group than in the control group (0.6±0.4 units vs. 1.2±0.8 units, p<0.001). Furthermore, variceal bleeding was significantly reduced in Child-Pugh class B patients treated with ligation compared with the control group ( p<0.05). Sixteen patients (25%) in the ligation group and 23 patients (36.5%) in the control group died. Comparison of Kaplan-Meier estimates of time to death for the two groups did not show significant differences ( p=0.19). More patients died of uncontrollable variceal bleeding in the control group (7 patients, 11%) than in the ligation group (3 patients, 4.7%) ( p=0.15). Conclusions: Although prophylactic ligation did not significantly reduce the first episode of bleeding from esophageal varices in cirrhotic patients with high-risk esophageal varices, a subgroup of patients (Child-Pugh class B) had a reduced frequency of the first episode of esophageal variceal bleeding after prophylactic banding ligation. Furthermore, there was a trend of reducing mortality from variceal bleeding in patients receiving prophylactic ligation. Prophylactic ligation is a promising treatment, but requires further investigation.

Upright posture decreases esophageal varices flow velocity in patients with cirrhosis

Background/Aims: Patients with cirrhosis tend to have esophageal variceal bleeding episodes at night, rather than during the day time. Since human beings carry on ordinary activities in the upright posture in the day time and are recumbent at night, we hypothesized that posture may be a factor related to a circadian variation of variceal bleeding. The aim of this study was to examine the effect of upright posture on esophageal varices hemodynamics in patients with cirrhosis. Methods: Nine patients with cirrhosis and esophageal varices were included in a crossover study performed on 2 separate days. On the non-endoscopic day, cardiac output, portal vein flow velocity, and superior mesenteric artery flow velocity were measured with percutaneous Doppler ultrasonography. Plasma renin activity and plasma norepinephrine concentrations were also determined. On the endoscopic day, in addition to the above measurements, esophageal varices flow velocity was measured using transesophageal Doppler ultrasonography. These measurements were performed in the supine position and 20 min after the assumption of the upright position. Results: On the non-endoscopic day, the upright posture significantly decreased cardiac output, portal vein flow velocity, and superior mesenteric artery flow velocity. Plasma renin activity and plasma norepinephrine concentration were significantly increased after assumption of the upright position. On the endoscopic day, similar hemodynamic and hormonal changes were observed. In addition, the upright posture significantly decreased esophageal varices flow velocity. Furthermore, the magnitude of the reduction in esophageal varices flow velocity (−42%) was significantly greater than that in portal vein flow velocity (−22%, p<0.01) and that in superior mesenteric artery flow velocity (−25%, p<0.01). Although the change in esophageal varices flow velocity was not significantly correlated with that in plasma renin activity ( r=−0.28) and that in plasma norepinephrine concentration ( r=−0.10), it was significantly correlated with the change in superior mesenteric artery flow velocity ( r=0.73, p<0.05). Conclusions: The upright posture decreases esophageal varices flow velocity mainly because of the reduction in splanchnic blood flow. This effect may contribute to a low prevalence of esophageal variceal bleeding in the day time in patients with cirrhosis

Prospective evaluation of esophageal varices in primary biliary cirrhosis: Development, natural history, and influence on survival

The aims of our prospective study were to determine the development and natural history of esophogeal varices and variceal bleeding in patients with primary biliary cirrhosis. As part of a controlled clinical study, 265 patients with primary biliary cirrhosis who did not have esophageal varices at entry were followed for a median of 5.6 yr. The mean age was 49 yr (range 26–75 yr), 89% were women, and 69% had advanced histologic stage disease (stage 3–4) on liver biopsy at study entry. All patients were screened annually for esophageal varices by barium esophogram or endoscopy, or both; endoscopy was used to diagnose all episodes of esophageal variceal bleeding. Esophageal varices developed in 83 (31%) patients, and 40 (48%) of those with esophageal varices experienced one or more episodes of esophageal variceal bleeding. Cox regression analysis indicated that only serum bilirubin and histologic stage were associated independently with time to development of esophageal varices. In patients who developed esophageal varices, 33% and 41% developed esophageal variceal bleeding at 1 and 3 yr, respectively. After development of esophageal varices, 1- and 3-yr survival estimates were 83% and 59%, respectively. After the initial variceal bleeding episode, survival estimates were 65% and 46% at 1 and 3 yr and were dependent on Child's classification. These findings are important in considering indications for prophylactic therapy for esophageal varices in primary biliary cirrhosis and may influence timing of liver transplantation.