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1.
J Hepatol ; 80(1): 73-81, 2024 01.
Article in English | MEDLINE | ID: mdl-37852414

ABSTRACT

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.


Subject(s)
Esophageal and Gastric Varices , Portasystemic Shunt, Transjugular Intrahepatic , Varicose Veins , Adult , Humans , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/surgery , Esophageal and Gastric Varices/drug therapy , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/prevention & control , Creatinine , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Varicose Veins/complications , Adrenergic beta-Antagonists/therapeutic use , Liver Cirrhosis/etiology , Sodium
2.
Gut ; 72(4): 749-758, 2023 04.
Article in English | MEDLINE | ID: mdl-36328772

ABSTRACT

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.


Subject(s)
End Stage Liver Disease , Esophageal and Gastric Varices , Hepatic Encephalopathy , Humans , Hepatic Encephalopathy/etiology , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/surgery , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Severity of Illness Index , Liver Cirrhosis/complications , Contraindications
3.
J Hepatol ; 75(2): 342-350, 2021 08.
Article in English | MEDLINE | ID: mdl-33845059

ABSTRACT

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.


Subject(s)
Antibiotic Prophylaxis/standards , Bacterial Infections/etiology , Esophageal and Gastric Varices/complications , Hemorrhage/etiology , Aged , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis/methods , Antibiotic Prophylaxis/statistics & numerical data , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Cephalosporins/pharmacology , Cephalosporins/therapeutic use , Esophageal and Gastric Varices/epidemiology , Female , Hemorrhage/epidemiology , Humans , Incidence , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Quinolones/pharmacology , Quinolones/therapeutic use , Risk Factors
4.
Hepatology ; 69(1): 282-293, 2019 01.
Article in English | MEDLINE | ID: mdl-30014519

ABSTRACT

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.


Subject(s)
Esophageal and Gastric Varices/surgery , Gastrointestinal Hemorrhage/surgery , Portasystemic Shunt, Transjugular Intrahepatic , Secondary Prevention/methods , Adult , Female , Humans , Male , Middle Aged , Prospective Studies , Recurrence , Risk Assessment , Treatment Failure , Treatment Outcome
5.
Clin Gastroenterol Hepatol ; 16(1): 132-139.e8, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28501536

ABSTRACT

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.


Subject(s)
Decision Support Techniques , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/mortality , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Risk Assessment/methods , Aged , Canada , Cohort Studies , Europe , Female , Humans , Male , Middle Aged , Severity of Illness Index , Survival Analysis
7.
Thromb Res ; 132(2): e99-e104, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23916380

ABSTRACT

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.


Subject(s)
Janus Kinase 2/genetics , Mutation , Venous Thrombosis/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Myeloproliferative Disorders/enzymology , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/pathology , Prognosis , Risk Factors , Splanchnic Circulation , Treatment Outcome , Venous Thrombosis/enzymology , Venous Thrombosis/pathology , Young Adult
8.
Am J Gastroenterol ; 107(12): 1872-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23007003

ABSTRACT

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.


Subject(s)
Esophageal and Gastric Varices/mortality , Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/mortality , Gastrointestinal Hemorrhage/therapy , Leukocyte Count , Portal Vein , Venous Thrombosis/complications , Acute Disease , Adult , Aged , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/surgery , Female , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Humans , Italy/epidemiology , Liver Cirrhosis/complications , Logistic Models , Male , Middle Aged , Prognosis , Prospective Studies , Recurrence , Risk Factors , Severity of Illness Index , Treatment Failure , Treatment Outcome
9.
J Clin Gastroenterol ; 46(7): 608-12, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22772740

ABSTRACT

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.


Subject(s)
Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/etiology , Hepatitis/epidemiology , Hepatitis/etiology , Liver Cirrhosis/complications , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/diagnosis , Esophageal and Gastric Varices/diagnosis , Female , Gastrointestinal Hemorrhage/diagnosis , Hepatitis/diagnosis , Hepatitis/mortality , Humans , Incidence , Liver Cirrhosis/etiology , Liver Neoplasms/diagnosis , Male , Middle Aged , Prognosis , Risk Factors
10.
Thromb Res ; 128(3): 233-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21497883

ABSTRACT

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.


Subject(s)
Janus Kinase 2/genetics , Venous Thrombosis/enzymology , Venous Thrombosis/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Risk Factors , Sex Factors , Young Adult
11.
Clin Appl Thromb Hemost ; 17(4): 367-70, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20530055

ABSTRACT

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.


Subject(s)
Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Liver Cirrhosis/immunology , Portal Vein , Thrombosis/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antiphospholipid Syndrome/complications , Female , Humans , Liver Cirrhosis/complications , Male , Middle Aged , Thrombosis/complications , Young Adult
13.
J Clin Gastroenterol ; 44(6): 448-51, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19730112

ABSTRACT

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.


Subject(s)
Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Liver Cirrhosis/complications , Portal Vein , Venous Thrombosis/drug therapy , Aged , Anticoagulants/administration & dosage , Female , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Male , Middle Aged , Treatment Outcome , Venous Thrombosis/etiology
14.
Mediterr J Hematol Infect Dis ; 1(3): e2009014, 2009 Nov 25.
Article in English | MEDLINE | ID: mdl-21415954

ABSTRACT

Portal vein thrombosis (PVT) not associated with hepatocellular carcinoma is considered a frequent complication of liver cirrhosis but, unlike PVT occurring in non-cirrhotic patients, very few data are available on its natural history and management. The reduced portal blood flow velocity is the main determinant of PVT but, as in other venous thromboses, multiple factors local and systemic, inherited or acquired often can concur with. PVT has a variety of clinical presentations ranging from asymptomatic to life-threatening diseases like gastroesophageal bleeding or acute intestinal ischemia. It is usually diagnosed by Doppler ultrasound but computed tomography and magnetic resonance imaging are useful to study the extent of thrombosis and the involvement of the abdominal organs. The risk of bleeding mainly determined by the presence of gastroesophageal varices and clotting alterations causes concern for the treatment of PVT in cirrhotic patients. To date, anticoagulant therapy seems to be indicated only in patients awaiting liver transplantation. This review focuses on the definition of the subgroups of patients with cirrhosis that might benefit from treatment of PVT and examines the pros and cons of the available treatments in terms of efficacy, monitoring and safety, providing also perspectives for future studies.

16.
Am J Gastroenterol ; 102(11): 2464-70, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17958760

ABSTRACT

OBJECTIVES AND METHODS: Splanchnic vein thrombosis (SVT), not associated with cancer or liver cirrhosis, is a rare event and scanty data are available on its natural history, long-term prognosis, and treatment. In this study 121 SVT patients consecutively seen from January 1998 to December 2005 were included and 95 of them were followed up for a median time of 41 months. Screening for thrombophilic factors was performed in 104 patients. New thrombotic or bleeding episodes were registered and anticoagulant therapy was performed according to preestablished criteria. RESULTS: SVT was an incidental finding in 34 (28.1%) patients; 34 (28.1%) presented with abdominal infarction; 39 (32.2%) had bowel ischemia or acute portal vein thrombosis; 14 (11.6%) had bleeding from portal hypertensive sources. Survival rates at 1, 3, and 7 yr were 95%, 93.3%, and 89.6%, respectively; 87.5% of deaths occurred at onset of SVT as complications of intestinal infarction. Patients with isolated portal vein thromboses had symptoms and intestinal infarction in 16/41 (39%) and 0/41 (0%) of the cases, respectively, whereas superior mesenteric vein thromboses, isolated or not, were associated with symptoms and intestinal infarction in 69/75 (92%) and 34/75 (45%), respectively. During the follow-up 14 (14.7%) suffered from 39 episodes of gastrointestinal bleeding with no deaths. A previous gastrointestinal bleed was associated with new hemorrhagic events during follow-up. New venous thrombotic episodes occurred in 10 of 95 patients (10.5%), of which 73% were in the splanchnic area. Seven out of these 10 patients had a chronic myeloproliferative disease (MPD) and none was on anticoagulation. CONCLUSIONS: Anticoagulant therapy was effective to obtain recanalization of acute SVT in 45.4% of patients and preserved patients from recurrent thrombosis when given lifelong.


Subject(s)
Splanchnic Circulation , Venous Thrombosis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Child , Child, Preschool , Combined Modality Therapy , Diagnostic Imaging , Female , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/epidemiology , Gastrointestinal Hemorrhage/therapy , Humans , Incidental Findings , Male , Middle Aged , Outcome Assessment, Health Care , Prognosis , Risk Factors , Venous Thrombosis/diagnosis , Venous Thrombosis/therapy
18.
J Med Genet ; 44(6): 412-6, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17307838

ABSTRACT

OBJECTIVE: To calculate the prevalence of common gain of function gene mutations in patients with different clinical manifestations of venous thromboembolism. DESIGN AND SETTING: Case-control study in two hospitals in Italy. PARTICIPANTS: 387 patients with venous thromboembolism and 286 controls. MAIN MEASURES: Factor V (FV) Leiden, factor II (FII) A20210 and JAK2 V617F mutations. RESULTS: Among patients with deep vein thrombosis in one leg, 23 (20.9%) carried FV Leiden and FII A20210 mutations. Similar figures were observed in patients with cerebral vein thrombosis (CVT; n = 9; 20.0%) and in patients presenting with splanchnic vein thrombosis (SVT; n = 26; 18.7%). A lower prevalence was obtained in patients with retinal vein thrombosis (n = 11; 11.8%). The JAK2 F617 mutant allele was found in 27 (21.1%) patients with SVT, but in none of the patients presenting with a thrombotic event from different districts. 13 of the 27 JAK2 V617F-positive subjects with SVT were previously known to have a myeloproliferative disease (MPD). Three other patients had a diagnosis of MPD after the occurrence of the thrombotic event. CONCLUSION: Carriership of FV Leiden or FII A20210 mutations identifies an at-risk condition for venous thrombosis in the lower extremities, SVT or CVT. In patients with SVT, screening for the JAK2 V617F mutation may be useful in recognising patients who should be carefully observed for the subsequent development of overt MPD. Thus, genetic tests may play a different role, various clinical manifestations of venous thromboembolism being associated with distinct risk profiles.


Subject(s)
Mutation/genetics , Thromboembolism/genetics , Venous Thrombosis/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Factor V/genetics , Female , Humans , Male , Middle Aged , Myeloproliferative Disorders/genetics , Prevalence , Prothrombin/genetics , Risk Factors
19.
Clin Lab ; 53(9-12): 583-9, 2007.
Article in English | MEDLINE | ID: mdl-18257465

ABSTRACT

The liver has a central role in the clotting process and an altered haemostasis is common in advanced liver disease. Nevertheless, recent studies have questioned the historical belief that impaired haemostasis in liver disease means an increased risk of bleeding. Coagulation and anticoagulation mechanisms are still balanced but are set at a lower level. Platelet function and number also play a role. The prevalence of thrombotic events is similar in both cirrhotic patients and in the general population but the cirrhotic patients have an increased risk for thrombosis in the splanchnic area. Portal blood flow stasis is the main underlying change favouring thrombosis even if other local, systemic, congenital and acquired factors are present. The onset of portal vein thrombosis strongly affects the prognosis of liver cirrhosis, worsening both portal hypertension and liver function. Some of the known risk factors for venous thrombosis--G20210A mutation of prothrombin, factor V Leiden, endoscopic treatment of esophageal varices and abdominal surgery--have a specific role in the development of splanchnic thrombosis in cirrhotic patients. The knowledge of the pathophysiological aspects of portal vein thrombosis and clotting alterations in liver disease will allow determination of the indication, duration and timing of anticoagulation therapy.


Subject(s)
Blood Coagulation Disorders/physiopathology , Liver Cirrhosis/blood , Portal Vein/pathology , Venous Thrombosis , Blood Coagulation Disorders/etiology , Blood Coagulation Factors/genetics , Blood Coagulation Factors/metabolism , Humans , Liver Cirrhosis/physiopathology , Splanchnic Circulation/physiology
20.
Blood Coagul Fibrinolysis ; 17(1): 59-61, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16607082

ABSTRACT

Budd-Chiari syndrome is a rare disease due to occlusion of the hepatic veins often presenting with acute liver failure. Common causes of Budd-Chiari syndrome are chronic myeloproliferative disorders, while acute leukemia has been associated with hepatic vein thrombosis in only two cases in the literature to date. We report a case of Budd-Chiari syndrome complicating a non-promyelocytic acute myelogenous leukemia leading to fulminant hepatic failure.


Subject(s)
Budd-Chiari Syndrome/etiology , Leukemia, Myeloid, Acute/complications , Liver Failure, Acute/etiology , Adult , Budd-Chiari Syndrome/diagnostic imaging , Fatal Outcome , Humans , Male , Tomography, X-Ray Computed
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