Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

BACKGROUND & AIMS: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.

Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding.

BACKGROUND: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE. PATIENTS AND METHODS: This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation. RESULTS: 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients. CONCLUSION: pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission.

The role of computed tomography for the prediction of esophageal variceal bleeding: Current status and future perspectives.

Esophageal variceal bleeding (EVB) is one of the most common and severe complications related to portal hypertension (PH). Despite marked advances in its management during the last three decades, EVB is still associated with significant morbidity and mortality. The risk of first EVB is related to the severity of both PH and liver disease, and to the size and endoscopic appearance of esophageal varices. Indeed, hepatic venous pressure gradient (HVPG) and esophagogastroduodenoscopy (EGD) are currently recognized as the "gold standard" and the diagnostic reference standard for the prediction of EVB, respectively. However, HVPG is an invasive, expensive, and technically complex procedure, not widely available in clinical practice, whereas EGD is mainly limited by its invasive nature. In this scenario, computed tomography (CT) has been recently proposed as a promising modality for the non-invasive prediction of EVB. Although CT is only a diagnostic modality, thus being not capable of supplanting EGD or HVPG in providing therapeutic and physiological data, it could potentially assist liver disease scores, HVPG, and EGD in a more effective prediction of EVB. However, to date, evidence concerning the role of CT in this setting is still lacking. Our review aimed to summarize and discuss the current evidence concerning the role of CT in predicting the risk of EVB.

Role of multidetector computed tomography angiography in non-variceal upper gastrointestinal bleeding: A comprehensive review.

Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common gastroenterological emergency associated with significant morbidity and mortality. Upper gastrointestinal endoscopy is currently recommended as the gold standard modality for both diagnosis and treatment, with computed tomography traditionally playing a limited role in the diagnosis of acute NVUGIB. Following the introduction of multidetector computed tomography (MDCT), this modality is emerging as a promising tool in the diagnosis of NVUGIB. However, to date, evidence concerning the role of MDCT in the NVUGIB diagnosis is still lacking. The aim of our study was to review the current evidence concerning the role of MDCT in the diagnosis of acute NVUGIB.

Severe Stenosis of Mitral Bioprosthetic Valve Thrombosis in a Patient with HCV-Related Cirrhosis and Duodenal Variceal Bleeding: The Deadly Triad.

Bioprosthetic valve thrombosis (BPVT) is considered a relatively rare but life-threatening clinical entity. Thus, there is the need of high clinical suspicion in order to make a timely diagnosis and related appropriate therapeutic interventions. In this regard, the management of BPVT is high risk, whatever the option taken (surgery and/or systemic fibrinolysis). The presence of severe comorbidities-as decompensated cirrhosis-further complicates the clinical decision-making process, calling for a patient-tailored integrated multidisciplinary approach. We report a challenging case of a 45-year-old patient with mitral bioprosthetic valve thrombosis and hepatitis C virus (HCV)-related cirrhosis complicated by active duodenal variceal bleeding.

Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis.

BACKGROUND & AIMS: Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis. METHODS: A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2,138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and a retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization. RESULTS: A total of 1,656 patients out of 1,770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio [OR] 3.1; 95% CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95% CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95% CI 1.8-3.8), nasogastric tube placement (OR 1.7; 95% CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95% CI 1.2-4.9). CONCLUSION: Bacterial infections develop in almost one-fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade. LAY SUMMARY: Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infections are the most frequent and occur early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

BACKGROUND & AIMS: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date. METHODS: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality. RESULTS: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not. CONCLUSIONS: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB. LAY SUMMARY: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.

Preemptive-TIPS Improves Outcome in High-Risk Variceal Bleeding: An Observational Study.

Patients admitted with acute variceal bleeding (AVB) and Child-Pugh C score (CP-C) or Child-Pugh B plus active bleeding at endoscopy (CP-B+AB) are at high risk for treatment failure, rebleeding, and mortality. A preemptive transjugular intrahepatic portosystemic shunt (p-TIPS) has been shown to improve survival in these patients, but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high-risk patients. This multicenter, international, observational study included 671 patients from 34 centers admitted for AVB and high risk of treatment failure. Patients were managed according to current guidelines, and use of drugs and endoscopic therapy (D+E) or p-TIPS was based on individual center policy. p-TIPS in the setting of AVB is associated with a lower mortality in CP-C patients compared with D+E (1 year mortality 22% vs. 47% in D+E group; P = 0.002). Mortality rate in CP-B+AB patients was low, and p-TIPS did not improve it. In CP-C and CP-B+AB patients, p-TIPS reduced treatment failure and rebleeding (1-year cumulative incidence function probability of remaining free of the composite endpoint: 92% vs. 74% in the D+E group; P = 0.017) and development of de novo or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion: p-TIPS must be the treatment of choice in CP-C patients with AVB. Because of the strong benefit in preventing further bleeding and ascites, p-TIPS could be a good treatment strategy for CP-B+AB patients.

Multicenter External Validation of Risk Stratification Criteria for Patients With Variceal Bleeding.

BACKGROUND & AIMS: Early placement of a transjugular intrahepatic portosystemic shunts (TIPS) is considered the treatment of choice for patients with acute variceal bleeding (AVB) and cirrhosis who have a high risk of death (Child-Pugh class B with active bleeding at endoscopy or Child-Pugh class C). It has been proposed that patients of Child-Pugh class B, even with active bleeding, should not be considered high risk. Alternative criteria have been proposed for identification of high-risk patients, such as Child-Pugh class C with plasma level of creatinine of 1 mg/dL or more (ChildC-C1) and a model for end-stage liver disease (MELD) score of 19 or more. We analyzed outcomes of a large cohort of patients with AVB who received the standard of care at different centers to validate these systems of risk stratification. METHODS: We performed an observational study of 915 patients with liver cirrhosis and AVB who received standard treatment (drugs, antibiotics, and endoscopic ligation, with TIPS as the rescue treatment), over different time periods between 2006 and 2014 in Canada and Europe. All patients were followed until day 42 (week 6) after index AVB or death. Child-Pugh and MELD scores were calculated at time of hospital admission. The primary outcome was mortality 6 weeks after index AVB among patients who met the early TIPS criteria (Child-Pugh class B with active bleeding at endoscopy or Child-Pugh class C), MELD19 criteria (patients with MELD scores of 19 or more), and ChildC-C1 criteria. RESULTS: Among 915 patients with AVB, 18% died within 6 weeks. Among the 523 patients who met the early TIPS criteria, 17% died within 6 weeks. All 3 rules discriminated patients at high risk of death from those with low risk: 28.3% of the patients classified as high risk by the early TIPS criteria died whereas only 7.0% of patients classified as low risk died; 46.0% of patients classified as high risk by the MELD19 criteria died vs 8.1% of patients classified as low risk; 51.9% of patients classified as high risk by the ChildC-C1 criteria died compared with 10.9% of patients classified as low risk. Mortality was significantly lower among patients with Child-Pugh class B (11.7%) than with Child-Pugh class C (35.6%) (P ≤ .001). Mortality was similar between patients with Child-Pugh class B cirrhosis with or without active bleeding (11.7%). Patients with Child-Pugh class A cirrhosis or MELD scores of 11 or less had low mortality (2%-4%), patients with Child-Pugh class B cirrhosis or MELD scores of 12 to 18 had intermediate mortality (10%-12%), and patients with Child-Pugh class C cirrhosis or MELD scores of 19 or more had high mortality (22%-46%). CONCLUSIONS: Patients with Child-Pugh class B cirrhosis and AVB who receive standard therapy, regardless of the presence of active bleeding, have 3-fold lower mortality than patients with Child-Pugh C cirrhosis and might not need TIPS. Patients with Child-Pugh class C and/or MELD scores of 19 or more should be considered at high risk of death. These findings might help refine criteria for early TIPS.

Nitric oxide metabolites, nitrative stress, and paraoxonase activity in hepatopulmonary syndrome.

AIM: To investigate possible abnormalities of vasoactive compounds, nitrative stress, and antioxidant activity of paraoxonase (PONa) in human hepatopulmonary syndrome (HPS), we determined endothelin-1 (ET), nitric oxide (NOx) metabolites, PONa alongside crude plasma nitrotyrosine (NT) as surrogate marker of nitrative stress. MATERIAL AND METHODS: Liver cirrhosis (LC) patients with HPS (n = 12) were matched by age, sex, and Child-Pugh score to LC patients without HPS (n = 15) and to healthy controls (CTR) (n = 15); plasma NO2(-) (nitrite) (vascular metabolite), NO3(-) (nitrate) (inflammatory metabolite), and PONa were determined by a colorimetric assay, ET, and NT by immunoassays. RESULTS: HPS patients showed higher level of ET (p = 0.0002), NO2(-) (p = 0.002), NO3(-) (p = 0.0001), NT (p < 0.0001), and lower PONa (p = 0.0004) than CTR; post-hoc analysis revealed greater ET (p < 0.05) and NO3(-) (p < 0.005) in LC patients with HPS than in LC patients without HPS. NT correlated to Child-Pugh score within HPS (p = 0.04) and LC (p = 0.02). CONCLUSION: Our HPS patients are characterized by elevated plasma levels of ET and NOx metabolites and lower PONa. Reduced PONa alongside elevated NO3(-) and NT suggests that defective antioxidation may favor nitrative stress and both may be implicated in the pathogenesis of HPS.

Outcome of patients with splanchnic venous thrombosis presenting without overt MPN: a role for the JAK2 V617F mutation re-evaluation.

INTRODUCTION: Although investigation for JAK2 V617F mutation is recommended in patients presenting with splanchnic venous thrombosis (SVT), no specific clinical advice is given to SVT patients presenting without myeloproliferative neoplasms (MPN) and JAK2 V617F mutation. In MPN-free SVT patients, to investigate the clinical outcome, the clinical impact of re-evaluation for the JAK2 V617F mutation, and relationships with the occurrence and time to diagnosis of MPN. MATERIALS AND METHODS: A cohort of non-cirrhotic SVT patients, enrolled at a single centre and prospectively analyzed. RESULTS: In 121 SVT patients prospectively followed from 1994 to 2012, a MPN was present in 28 (23.1%). Additional 13 patients (10.7%) showed only the JAK2 V617F mutation. During the follow-up, the JAK2 V617F mutation and/or MPN were identified in 8 patients (median time of development: 21 months, range 6-120), whereas 72 remained (MPN and JAK2 V617F)-free until the end of the observation. The mortality rate was higher among patients presenting with MPN and/or the JAK2 V617F mutation than in patients who developed later or remained disease-free (p=0.032). The thrombosis-free survival was lower in patients with (p=0.04) or developing later MPN and the JAK2 V617F mutation (p=0.005) than in patients (MPN and JAK2 V617F)-free. The incidence of bleeding was similar among groups. CONCLUSIONS: MPN with or without circulating positive clones for JAK2 V617F mutation can occur long after a SVT, identifying at risk patients for new thrombotic events. If confirmed in other studies, re-evaluation for JAK2 V617F mutation may be of help in early MPN detection and clinical management of SVT patients.

Splanchnic vein thrombosis and variceal rebleeding in patients with cirrhosis.

OBJECTIVES: Splanchnic vein thrombosis (SVT) affects the short-term prognosis of acute variceal bleeding in cirrhotic patients. This study evaluated whether SVT also affects the rebleeding rate of patients included in a program of secondary prophylaxis after variceal bleeding. PATIENTS AND METHODS: A total of 387 patients with variceal bleeding were included from January 2001 to December 2010. Band ligation was carried out every 3-4 weeks. Follow-up included endoscopy at 1, 3, and every 6 months, Echo-Doppler, and biochemical examination every 6 months. From 2005, patients with SVT received anticoagulation with enoxaparin 200 UI/kg/day for at least 6 months. The therapy was started after variceal eradication. RESULTS: SVT was diagnosed in 41 patients at variceal bleeding, in eight before and in 18 patients during the follow-up. Variceal eradication was achieved in 89.2 and 86.6% in no-SVT and SVT patients. Rebleeding occurred in 9.5 and 11.9% of no-SVT and SVT patients at 12 months. Varices relapsed more frequently in SVT than in no-SVT patients (25.4 vs. 14.67%, P=0.03). The rates of variceal rebleeding and relapse were similar in patients who received or did not receive anticoagulation, but mortality was significantly lower in patients who received anticoagulation. CONCLUSION: SVT favors the relapse of esophageal varices, but rebleeding can be effectively prevented by standard scheduled band ligations. Anticoagulation does not prevent variceal relapse. The improvement in the survival of patients treated with anticoagulation needs to be confirmed in future studies.

The effectiveness of current acute variceal bleed treatments in unselected cirrhotic patients: refining short-term prognosis and risk factors.

OBJECTIVES: The mortality from esophageal variceal hemorrhage in liver cirrhosis patients remains approximately 15-20%. Predictors of short-term outcomes, such as the hepatic venous pressure gradient, are often unavailable in the acute setting. Clinical variables seem to have a similar predictive performance, but some variables including active bleeding during endoscopy have not been reevaluated after the utilization of endoscopic banding as endoscopic procedure. In addition, patients with severe liver failure are often excluded from clinical trials. The aim of this study was to prospectively reevaluate the risk factors affecting a 5-day failure after acute variceal bleeding in unselected cirrhotic patients, managed with the current standard treatment using vasoactive drugs, band ligation, and antibiotics. METHODS: One hundred and eighty five patients with liver cirrhosis and variceal bleeding admitted from January 2010 to July 2011 were evaluated. RESULTS: Hepatocellular carcinoma was present in 28.1% of cases and portal vein thrombosis (PVT) was present in 17.3% of cases. Band ligation was feasible in 92.4% of cases. Five-day failure occurred in 16.8% of cases; 12 patients (6.5%) experienced failure to control bleeding or early rebleeding, and 66.7% of patients died within 5 days. The overall 5-day mortality rate was 14.6%. By multivariate analysis, we determined that Child-Pugh class C, a white blood cell count over 10 × 10(9)/l, and the presence of PVT were the only independent predictors of the 5-day failure. CONCLUSIONS: The prognosis of a consistent group of liver cirrhosis patients with variceal bleeding remains poor. The current treatment is highly effective in controlling variceal bleeding, but mortality is related mainly to the severity of liver failure.

Hypoxic hepatitis occurring in cirrhosis after variceal bleeding: still a lethal disease.

BACKGROUND: Hypoxic hepatitis (HH) occurring after gastrointestinal bleeding in cirrhotic patients has been scarcely studied and is reported as a rare occurrence carrying a severe prognosis. The management of bleeding from esophageal varices (BEV) and similarly the prognosis has improved in the last decades. GOALS: To evaluate retrospectively the incidence, clinical features, risk factors, and outcome of HH occurring in cirrhotic patients with BEV treated with the current standard therapy. Cirrhotics with BEV consecutively admitted from 2004 to 2008 were considered. Standard therapy consisted of intensive care support, somatostatin, antibiotics, and band ligation. HH was diagnosed if an elevation of alanine aminotransferase >10-fold from basal occurred. RESULTS: Among 349 patients admitted for BEV, 24 (6.8%) had HH. Most patients were over 60 years old and had advanced liver disease; 41.7% had hepatocellular carcinoma, and 29.2% had portal vein thrombosis (PVT). Hypovolemic shock occurred in 16 (66.7%) patients, and failure to control initial bleeding in 12 (50%) patients. The 6-week mortality rate was 83.3% in HH compared with 24.6% in non-HH patients. Causes of death were massive bleeding in 4, hepatic encephalopathy in 7, and renal failure in 9. Binary logistic regression analysis showed that failure to control initial bleeding, diabetes, and PVT were factors independently associated with the development of HH. CONCLUSIONS: HH occurring in cirrhosis with gastrointestinal bleeding still carries an ominous prognosis. The severity of hemorrhage as expressed by failure to control bleeding contributes heavily to HH; in addition, the presence of PVT and diabetes further compromising the hepatic circulatory reserve may favor hypoxic damage.

Sex modulation of the occurrence of jak2 v617f mutation in patients with splanchnic venous thrombosis.

BACKGROUND: The JAK2 V617F mutation is an independent risk factor for MPN and SVT. Gender-related differences in MPN distribution have been reported and, recently, variability in the JAK2 V617F allele burden between sexes has been suggested. We wondered whether gender would modulate the role of the JAK2 V617F mutation as susceptibility risk factor for SVT. MATERIALS AND METHODS: In 180 patients presenting with SVT, medical history was collected. The presence of the JAK2 V617F mutation and 46/1 haplotype was determined by polymerase chain reaction followed by TaqMan SNP genotyping assays. RESULTS: Among patients with SVT, 43 (23.9%; 95%-CI: 18.2-30.7) carried the JAK2 V617F mutation. The JAK2 V617F mutation was found more frequently in women (29/95: 30.5%; 95%-CI: 22.1-40.4) than in men (14/85: 16.5%; 95%-CI: 10.0-25.9; OR: 2.2; 95%-CI: 1.1-4.5). The distribution of 46/1 haplotype frequencies did not differ significantly between men and women. In women carrying the rs12343867 CC genotype, the frequency observed for the occurrence of the V617F mutation was significantly higher than that observed in those not carrying (60.0% [95% CI: 31.2-83.3] vs. 26.8% [95% CI: 18.4-37.4]; OR: 4.1; 95%-CI: 1.1-14.9). In men, a similar prevalence was found among carriers of the rs12343867 CC genotype (16.7% [95% CI: 3.5-46.0]) and in non carriers (16.4% [95% CI: 9.3-27.2]). The V617F allele burden was unrelated to clinical characteristics and significantly higher in carriers of the rs12343867 CC genotype. CONCLUSIONS: Present findings suggest that, in patients presenting with SVT, the JAK2 V617F mutation is frequently found in women and, possibly by interacting with the 46/1 haplotype, may represent a gender-related susceptibility allele for SVT.

Antiphospholipid antibodies and antiphospholipid syndrome: role in portal vein thrombosis in patients with and without liver cirrhosis.

UNLABELLED: The antiphospholipid syndrome (APS) has been associated with portal vein thrombosis (PVT). This study explored the contribution of antiphospholipid antibodies (aPL) to PVT in cirrhotic and noncirrhotic patients. PATIENTS AND METHODS: A total of 50 patients with liver cirrhosis and PVT, 50 patients with liver cirrhosis without PVT, 50 consecutive PVT without liver cirrhosis, and 50 controls. aPL tests: lupus anticoagulants (LAs), immunoglobulin G (IgG) anti-cardiolipin antibodies (aCL), IgG anti-beta-2-glycoprotein-I (ß(2)GPI), and IgG ß( 2)GPI-complexed with oxidized low-density lipoprotein antibodies (ox-LDL). RESULTS: Lupus anticoagulants were negative in all patients. A titre of IgG aCL >40 IgG phospholipid units (GPL) was present in 2% of patients with liver cirrhosis and in none of the other groups. In all, 4% of patients with PVT without cirrhosis were positive for IgG ß(2)GPI in the absence of any other positive aPL and labelled as primary APS. CONCLUSIONS: aPL play no role in PVT associated with liver cirrhosis but can be tested in idiopathic PVT.

Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis.

BACKGROUND: Treatment of portal vein thrombosis (PVT) in patients with liver cirrhosis is not well established. AIM: We intended to assess the safety and efficacy of low molecular weight heparin (LMWH) to treat PVT in cirrhotic patients. STUDY: All 39 patients diagnosed with non-neoplastic PVT and cirrhosis from June 2005 to December 2006 were evaluated for anticoagulation therapy (AT). PVT was occludent in 15.4%, partial in 64.1%, and portal cavernoma presented in 20.5%. Twenty-eight patients received 200 U/kg/d of enoxaparin for at least 6 months. In 39.3% of patients PVT was an occasional finding, in 10.7% presented with acute abdominal pain, in 50% with bleeding from gastroesophageal varices. In this last group LMWH was started after endoscopic eradication of varices by band ligation. RESULTS: Complete recanalization of portal vein occurred in 33.3%, partial recanalization in 50% and no response in 16.7% of patients. Further 12 patients who continued AT obtained complete recanalization at a median time of 11 months (range 7 to 17 mo). Overall, a complete response was obtained in 75% of patients. No significant side effects, particularly bleeding complications, were observed during the treatment. CONCLUSIONS: LMWH demonstrated safe and effective in the treatment of PVT in patients with liver cirrhosis.