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A total of 2%-10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement-mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver-related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non-PNH cohort. Sixty-two patients (33 women), median age 35 years (28-48) and median follow-up VLD diagnosis 4.7 years (1.2-9.5), were included. Clone size was 80% (70-90), median hemoglobin concentration was 10.0 g/dl (8-11), and lactate dehydrogenase (LDH) was 736 IU (482-1744). Forty-two patients (68%) had eculizumab; median exposure time was 40.1 [9.3-72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1-0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07-0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six-year thrombosis-free survival was 70%, 95% CI [0.60-0.83] for PNH cohort and 83%, 95% CI [0.70-1.00] for non-PNH Envie 2 patients, (p < .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non-PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD., (© 2022 Wiley Periodicals LLC.)

In the past, patients with liver cirrhosis were thought to be prone to increased bleeding risk. However, those with compensated liver cirrhosis actually have normal coagulative balance, which can become altered when liver function worsens, or infection, bleeding, or acute kidney insufficiency occur. When this happens, it is now recognized that patients with liver cirrhosis are at higher risk of thrombotic rather than haemorrhagic complications. Anticoagulation plays a favourable role both when used therapeutically or prophylactically. Successful anticoagulation is associated with a lower rate of decompensation and with improved survival. To date, treatment has involved the use of low molecular weight heparins and vitamin K antagonists. Preliminary data suggest that novel non-vitamin K antagonist oral anticoagulants can be used safely in patients with liver cirrhosis., (© 2019 The Author(s).)

Hepatic veno-occlusive disease (HVOD), alias sinusoidal obstruction syndrome, may develop as a complication of chemotherapy in the setting of hematopoietic stem cell transplantation. HVOD is less frequently described after exposure to chemotherapy in the nontransplant setting and can also be a complication after ingestion of toxins, such as pyrrolizidine alkaloids. Veno-occlusive disease may also affect the lungs, and it is therefore termed pulmonary veno-occlusive disease (PVOD). Similarly, PVOD can develop after exposure to chemotherapeutic agents in the treatment of solid and hematological malignancies. In addition, PVOD has also been linked to autoimmune disorders and occupational solvent exposure. Finally, the heritable form of PVOD is due to biallelic mutations of the EIF2AK4 gene. Both HVOD and PVOD share common histopathological features and pathophysiologic mechanisms. Both clinical disorders are rare complications that can appear after exposure to the common inciting trigger of chemotherapeutic agents. The present review aims to summarize the current knowledge of HVOD and PVOD and to describe both similarities as well as differences regarding both conditions., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

In real-world clinical practice, the acceptance of anticoagulation therapy in the management of portal vein thrombosis (PVT) in patients with cirrhosis is limited by the fear of an increased bleeding risk. Additionally, accumulating evidence indicates that spontaneous recanalization of PVT may occur in the absence of antithrombotic treatment. Therefore, risk stratification based on outcomes in such patients is crucial for determining a therapeutic strategy. In this paper, we draw attention to the distinct clinical entity, "transient PVT" by introducing two cases with PVT that spontaneously recanalized in the absence of antithrombotic treatment. We reviewed the available data regarding the probability of and predictors for spontaneous recanalization of PVT. Available data suggest singling out transient thrombosis in the natural history of PVT in patients with cirrhosis because of its prognostic and management implications.

Background: The outcome of cholangiopathy developing in intensive care unit (ICU) is not known in patients surviving their ICU stay., Aim: To perform a survey in liver units, in order to clarify the course of cholangiopathy after surviving ICU stay., Methods: The files of the liver units affiliated to the French network for vascular liver disease were screened for cases of ICU cholangiopathy developing in patients with normal liver function tests on ICU admission, and no prior history of liver disease., Results: Between 2005 and 2015, 16 cases were retrieved. Extensive burns were the cause for admission to ICU in 11 patients. Serum alkaline phosphatase levels increased from day 11 (2-46) to a peak of 15 (4-32) × ULN on day 81 (12-511). Magnetic resonance cholangiography showed irregularities or frank stenosis of the intrahepatic ducts, and proximal extrahepatic ducts contrasting with a normal aspect of the distal common bile duct. Follow-up duration was 20.6 (4.7-71.8) months. Three patients were lost to follow-up; 2 patients died from liver failure and no patient was transplanted. One patient had worsening strictures of the intrahepatic bile ducts with jaundice. Nine patients had persistent but minor strictures of the intrahepatic bile ducts on MR cholangiography, and persistent cholestasis without jaundice. One patient had normal liver function tests., Conclusions: In patients surviving their ICU stay, ICU cholangiopathy is not uniformly fatal in the short term or clinically symptomatic in the medium term. Preservation of the distal common bile duct appears to be a finding differentiating ICU cholangiopathy from other diffuse cholangiopathies., (© 2017 John Wiley & Sons Ltd.)

Background: China may have the largest number of Budd-Chiari syndrome (BCS) cases in the world (at least 1914 original papers were published, and at least 20 191 BCS patients were reported). Considering the discrepancy in the clinical profiles and preferred treatment selection of primary BCS between the West and China, understanding its aetiology in these two different regions is very important., Aim: To review the data from large cohort studies and meta-analyses to illustrate the epidemiology of risk factors for BCS in the West and China., Methods: Relevant papers were identified by major English- and Chinese-language databases, conference abstracts, and by manual search., Results: Risk factors reviewed include myeloproliferative neoplasms (MPNs) and their related gene mutations, anti-phospholipid syndrome, paroxysmal nocturnal haemoglobinuria (PNH), hyperhomocysteinaemia and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation, factor V Leiden (FVL) and prothrombin G20210A mutations, inherited anti-thrombin, protein C and protein S deficiencies, pregnancy and puerperium, poverty, and family history., Conclusions: We examined the differences in the aetiological distribution of BCS between the West and China. Several recommendations should be considered in Chinese BCS patients: (i) screening for hyperhomocysteinaemia and MTHFR mutation should be regularly performed; (ii) screening for MPNs, PNH, and anti-phospholipid syndrome should be selectively performed; (iii) inherited anti-thrombin, protein C, and protein S deficiencies should be actively explored; (iv) screening for FVL and prothrombin G20210A mutations may be unnecessary; and (v) the clinical significance of pregnancy and puerperium, poverty with bacterial infections and unsanitary environments, and family history as possible risk factors should never be neglected., (© 2016 John Wiley & Sons Ltd.)

Background: Supra-mesocolic surgery (SMS) is complicated in patients with portal vein cavernoma (PC) and portal decompression is recommended. The aim of this study was to report a large single centre of SMS in patients with PC without portal decompression., Methods: Between 2006 and 2013, all patients who met inclusion criteria were analyzed retrospectively. The primary endpoint was the feasibility rate, surgical and postoperative outcome. The secondary endpoints were the long-term outcome of patients who underwent biliary bypass for cholangitis. Risk factors for complications were studied., Results: Thirty patients underwent 51 procedures. Pancreatitis was the main etiology of PC (19/30) and biliary obstruction was mainly related to the underlying disease and not to portal cholangiopathy (12/14). All planned procedures were successfully completed. Fourteen patients underwent biliary bypass. Median blood loss (250 ml), transfusion (n = 7), mortality (n = 0), overall morbidity (n = 12) and the median hospital stay (10 days). Good long-term control of cholangitis was achieved in the 9 patients alive with available follow-up. Significant risk factors for complications were a previous abdominal wall scar, previous intra-abdominal surgical field and liver fibrosis., Conclusion: SMS can be safely performed in patients with PC. In patients with risk factors for complications, portal decompression should be discussed., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Aim: To study the clinical presentation of Budd-Chiari syndrome (BCS) and identify the aetiologies of this disease in Algeria., Methods: Patients with BCS, hospitalised in our unit from January 2004 until June 2010 were included and the aetiological factors were assessed. Patients presenting a BCS in the setting of advanced-stage cirrhosis or a liver transplantation were excluded from the study. The diagnosis was established when an obstruction of hepatic venous outflow (thrombosis, stenosis or compression) was demonstrated. We diagnosed myeloproliferative disease (MPD) by bone marrow biopsy and V617F JAK2 mutation. Anti-phospholipid syndrome (APLS) was detected by the presence of anticardiolipin antibodies, anti-β2 glycoprotein antibodies and Lupus anticoagulant. We also detected paroxysmal nocturnal haemoglobinuria (PNH) by flow cytometry. Celiac disease and Behçet disease were systematically investigated in our patients. Hereditary anticoagulant protein deficiencies were also assessed. We tested our patients for the G20210A mutation at Beaujon Hospital. Imaging procedures were performed to determine a local cause of BCS, such as a hydatid cyst or a liver tumour., Results: One hundred and fifteen patients were included. Mean follow up: 32.12 mo. Mean age: 34.41 years, M/F = 0.64. Chronic presentation was frequent: 63.5%. The revealing symptoms for the BCS were ascites (74.8%) and abdominal pain (42.6%). The most common site of thrombosis was the hepatic veins (72.2%). Involvement of the inferior vena cava alone was observed in 3 patients. According to the radiological investigations, BCS was primary in 94.7% of the cases (n = 109) and secondary in 5.2% (n = 6). An aetiology was identified in 77.4% of the patients (n = 89); it was multifactorial in 27% (n = 31). The predominant aetiology of BCS in our patients was a myeloproliferative disease, observed in 34.6% of cases. APLS was found in 21.7% and celiac disease in 11.4%. Other acquired conditions were: PNH (n = 4), systemic disease (n = 6) and inflammatory bowel disease (n = 5). Anticoagulant protein deficiency was diagnosed in 28% of the patients (n = 18), dominated by protein C deficiency (n = 13). Secondary BCS was caused by a compressing hydatic cyst (n = 5) and hepatocellular carcinoma (n = 1)., Conclusion: The main aetiologic factor of BCS in Algeria is MPD. The frequency of celiac disease justifies its consideration when BCS is diagnosed in our region.

Portal cavernoma cholangiopathy (PCC) is defined as abnormalities in the extrahepatic biliary system including the cystic duct and gallbladder with or without abnormalities in the 1st and 2nd generation biliary ducts in a patient with portal cavernoma. Presence of a portal cavernoma, typical cholangiographic changes on endoscopic or magnetic resonance cholangiography and the absence of other causes of these biliary changes like bile duct injury, primary sclerosing cholangitis, cholangiocarcinoma etc are mandatory to arrive a diagnosis. Compression by porto-portal collateral veins involving the paracholedochal and epicholedochal venous plexuses and cholecystic veins and ischemic insult due to deficient portal blood supply or prolonged compression by collaterals bring about biliary changes. While the former are reversible after porto-systemic shunt surgery, the latter are not. Majority of the patients with PCC are asymptomatic and approximately 21% are symptomatic. Symptoms in PCC could be in the form of long standing jaundice due to chronic cholestasis, or biliary pain with or without cholangitis due to biliary stones. Endoscopic retrograde cholangiography has no diagnostic role because it is invasive and is associated with risk of complications, hence it is reserved for therapeutic procedures. Magnetic resonance cholangiography and portovenography is a noninvasive and comprehensive imaging technique, and is the modality of choice for mapping of the biliary and vascular abnormalities in these patients. PCC is a progressive condition and symptoms develop late in the course of portal hypertension only in patients with severe or advanced changes of cholangiopathy. Asymptomatic patients with PCC do not require any treatment. Treatment of symptomatic PCC can be approached in a phased manner, coping first with biliary clearance by nasobiliary or biliary stent placement for acute cholangitis and endoscopic biliary sphincterotomy for biliary stone removal; second, with portal decompression by creating portosystemic shunt; and third, with persistent biliary obstruction by performing second-stage biliary drainage surgery such as hepaticojejunostomy or choledochoduodenostomy. Patients with symptomatic PCC have good prognosis after successful endoscopic biliary drainage and after successful shunt surgery.

Objective: It has been suggested that HIV infection has a detrimental impact on patients with hepatocellular carcinoma (HCC). The present study sought to test this hypothesis, while controlling for tumor extension and liver disease., Design and Setting: A case control and a cohort approach were performed in patients with HCC managed prospectively via dedicated multidisciplinary team meeting in a single tertiary institution between 2004 and 2009., Subjects: Of 473 consecutive treatment-naive patients with HCC, 23 were HIV-positive (HIV) and 450 were HIV-negative (HIV). HIV patients were matched 1:2 with a control group of HIV patients in terms of the etiology of HCC, the severity of liver disease, tumor extension, and year of diagnosis., Intervention: Curative or palliative treatment of HCC., Main Outcome Measures: Eligibility for HCC treatment, the treatment actually administered, and the survival rate., Results: The HIV population was younger than the HIV population (mean age: 49 vs. 61 years, respectively; P < 0.0001). Curative treatment was recommended by the multidisciplinary team meeting and then actually performed to a similar extent in HIV patients (74% and 43%, respectively) and their matched HIV controls (74% and 56%, respectively). The HIV and their matched HIV patients did not differ significantly in terms of the 3-year survival rate [44% vs. 48%, respectively; mean (95% confidence interval) hazard ratio = 0.64 (0.3-1.3); P = 0.2]. In a cohort analysis, HIV status was not an independent predictor of survival among curatively treated patients., Conclusion: In an equal-access unbiased environment, HIV status does not significantly influence treatment access, delivery, and outcome.

Myeloproliferative neoplasms (MPNs) are the most common cause of Budd-Chiari syndrome (BCS) and nonmalignant, noncirrhotic portal vein thrombosis (PVT). In this meta-analysis, we determined the prevalence of MPNs and their subtypes as well as JAK2V617F and its diagnostic role in these uncommon disorders. MEDLINE and EMBASE databases were searched. Prevalence of MPNs, JAK2V617F, and MPN subtypes were calculated using a random-effects model. A total of 1062 BCS and 855 PVT patients were included. In BCS, mean prevalence of MPNs and JAK2V617F was 40.9% (95% CI, 32.9%-49.5%) and 41.1% (95% CI, 32.3%-50.6%), respectively. In PVT, mean prevalence of MPNs and JAK2V617F was 31.5% (95% CI, 25.1%-38.8%) and 27.7% (95% CI, 20.8%-35.8%), respectively. JAK2V617F and MPNs were more frequent in BCS compared with PVT (P = .03 and P = .09, respectively). Polycythemia vera was more prevalent in BCS than in PVT (P = .001). JAK2V617F screening in splanchnic vein thrombosis (SVT) patients without typical hematologic MPN features identified MPN in 17.1% and 15.4% of screened BCS and PVT patients, respectively. These results demonstrate a high prevalence of MPNs and JAK2V617F in SVT patients and show differences in underlying etiology between these disorders. Furthermore, these results validate routine inclusion of JAK2V617F in the diagnostic workup of SVT patients.

Decreased levels of most coagulation factors and thrombocytopenia are the main haemostatic abnormalities of cirrhosis. As a consequence, this condition was, until recently, considered as the prototype acquired coagulopathy responsible for bleeding. However, recent evidence suggests that it should, rather, be regarded as a condition associated with normal or even increased thrombin generation. The bleeding events that occur in these patients should, therefore, be explained by the superimposed conditions that frequently occur in this setting. Due to elevated levels of factor VIII (procoagulant driver) in combination with decreased protein C (anticoagulant driver), which are typically found in patients with cirrhosis, a procoagulant imbalance, defined as a partial resistance to the in vitro anticoagulant action of thrombomodulin, can be demonstrated. Whether this in vitro hypercoagulability is truly representative of what occurs in vivo remains to be established. However, the hypothesis that it may have clinical consequences is attractive and deserves attention. The possible consequences that we discuss herein include whether (i) cirrhosis is a condition associated with increased risk of venous thromboembolism or portal vein thrombosis; (ii) the hypercoagulability associated with cirrhosis has any other role outside coagulation (i.e. progression of liver fibrosis); and (iii) anticoagulation should be used in cirrhosis. Although apparently provocative, considering anticoagulation as a therapeutic option in patients with cirrhosis is now supported by a rationale of increasing strength. There may be subgroups of patients who benefit from anticoagulation to treat or prevent thrombosis and to slow hepatic fibrosis. Clinical studies are warranted to explore these therapeutic options., (© 2011 International Society on Thrombosis and Haemostasis.)

The germline JAK2 46/1 haplotype has been associated with the development of JAK2(V617F)-positive as well as JAK2(V617F)-negative myeloproliferative neoplasms (MPNs). In this study we examined the role of the 46/1 haplotype in the etiology and clinical presentation of patients with splanchnic vein thrombosis (SVT), in which MPNs are the most prominent underlying etiological factor. The single-nucleotide polymorphism rs12343867, which tags 46/1, was genotyped in 199 SVT patients. The 46/1 haplotype was overrepresented in JAK2(V617F)-positive SVT patients compared with controls (P < .01). Prevalence of the 46/1 haplotype in JAK2(V617F)-negative SVT patients did not differ from prevalence in the controls. However, JAK2(V617F)-negative SVT patients with a proven MPN also exhibited an increased frequency of the 46/1 haplotype (P = .06). Interestingly, 46/1 was associated with increased erythropoiesis in JAK2(V617F)-negative SVT patients. We conclude that the 46/1 haplotype is associated with the development of JAK2(V617F)-positive SVT. In addition, our findings in JAK2(V617F)-negative SVT patients indicate an important role for the 46/1 haplotype in the etiology and diagnosis of SVT-related MPNs, independent of JAK2(V617F), that requires further exploration.

Pulmonary embolism occurs more frequently after hepatectomy than previously thought but is infrequently associated with peripheral deep vein thrombosis. In this paper, we report 2 cases of postoperative hepatic vein thrombosis after liver resection. Both patients had undergone major hepatectomy of a non-cirrhotic liver largely exposing the middle hepatic vein. Clots were incidentally found in the middle hepatic vein 4 and 17 d after surgery despite routine systemic thrombo-prophylaxis with low molecular weight heparin. Coagulation of the transition plan in a context of mutation of the prothrombin gene and inflammation induced biloma were the likely predisposing conditions. Clots disappeared following curative anticoagulation. We conclude that thrombosis of hepatic veins may occur after liver resection and is a potential source of pulmonary embolism.

Bloodstream infections (BSIs) are a major cause of mortality in liver transplant recipients. The incidence, microbiology, and outcome of BSIs in the first year after liver transplantation were analyzed in 704 patients who underwent transplantation at a single center between 1997 and 2007. BSIs occurred in 205 (29.1%) of the 704 patients. Overall, 259 episodes were documented, and they resulted in an incidence rate of 36.8%. Of these episodes, 39.4%, 27.8%, 17%, and 15.8% occurred in the very early period (< or = 10 days after liver transplantation), the early period (days 11-30), the intermediate period (days 31-90), and the late period (days 91-365), respectively. The most frequent pathogens were Enterobacteriaceae members (41%), Staphylococcus aureus (19.8%), enterococci (13.1%), Pseudomonas aeruginosa (8.8%), and yeasts (7.1%). The median time of onset ranged from 7 days for methicillin-resistant S. aureus to 25 days for Enterobacteriaceae. Mortality at 15 days after BSIs was 16.2%. Kaplan-Meier survival curves showed that patients with BSIs had a significantly higher 1-year mortality rate than those without BSIs (28.3% versus 16.6%, P < 0.001 with the log-rank test). When the time of BSI onset was considered, 1-year mortality was significantly associated with very early and early episodes (P < 0.001) but not with intermediate and late episodes (P = 0.47). In conclusion, BSIs are frequent and early complications after liver transplantation and are mostly caused by gram-negative bacilli. A BSI in the first posttransplant month is a significant predictor of 1-year survival.

In Budd-Chiari syndrome (BCS), thrombosis develops in the hepatic veins or inferior vena cava. To study the relationship between hypofibrinolysis and BCS, we measured plasma levels of fibrinolysis proteins in 101 BCS patients and 101 healthy controls and performed a plasma-based clot lysis assay. In BCS patients, plasminogen activator inhibitor 1 (PAI-1) levels were significantly higher than in controls (median, 6.3 vs 1.4 IU/mL, P < .001). Thrombin-activatable fibrinolysis inhibitor and plasmin inhibitor levels were lower than in controls (13.8 vs 16.9 microg/mL and 0.91 vs 1.02 U/L, both P < .001). Median plasma clot lysis time (CLT) was 73.9 minutes in cases and 73.0 minutes in controls (P = .329). A subgroup of cases displayed clearly elevated CLTs. A CLT above the 90th or 95th percentile of controls was associated with an increased risk of BCS, with odds ratios of 2.4 (95% confidence interval, 1.1-5.5) and 3.4 (95% confidence interval, 1.2-9.7), respectively. In controls, only PAI-1 activity was significantly associated with CLT. Analysis of single nucleotide polymorphisms of fibrinolysis proteins revealed no significant differences between cases and controls. This case-control study provides the first evidence that an impaired fibrinolytic potential, at least partially caused by elevated PAI-1 levels, is related to the presence of BCS.

Myeloproliferative diseases (MPDs) represent the commonest cause of splanchnic vein thrombosis (SVT), including Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT), but their diagnosis is hampered by changes secondary to portal hypertension, while their influence in the outcome of SVT remains unclear. We assessed the diagnostic and prognostic value of JAK2 and MPL515 mutations in 241 SVT patients (104 BCS, 137 PVT). JAK2V617F was found in 45% of BCS and 34% of PVT, while JAK2 exon 12 and MPL515 mutations were not detected. JAK2V617F was found in 96.5% of patients with bone marrow (BM) changes specific for MPD and endogenous erythoid colonies, but also in 58% of those with only one feature and in 7% of those with neither feature. Stratifying MPD diagnosis first on JAK2V617F detection would have avoided BM investigations in 40% of the patients. In BCS, presence of MPD carried significantly poorer baseline prognostic features, required hepatic decompression procedures earlier, but had no impact on 5-year survival. Our results suggest that JAK2V617F testing should replace BM investigations as initial test for MPD in patients with SVT. Underlying MPD is associated with severe forms of BCS, but current therapy appears to offset deleterious effects of MPD on the medium-term outcome.

Background: The best technique to estimate portal hypertension (PHT) is to measure the hepatic venous pressure gradient (HVPG), which is an invasive method., Aim: To assess the relationship between the Fibrotest (Biopredictive, Paris, France) and the presence and degree of PHT in patients with liver disease, and to determine if the Fibrotest can diagnose severe PHT, defined by HVPG >or= 12 mmHg, in cirrhotic patients., Methods: Patients who underwent a transjugular liver biopsy were prospectively included. HVPG was measured, and classification of histological lesions assessed. The same day, blood samples for Fibrotest were performed., Results: A total of 130 patients were included (no or minimal fibrosis: 12%, moderate fibrosis 17%, cirrhosis 71%). There was a significant correlation between Fibrotest and HVPG (Pearson correlation coefficient = 0.58, P < 0.0001), also weaker in cirrhotic patients (Pearson correlation coefficient = 0.24, P = 0.02). In cirrhotic patients, Fibrotest was significantly higher when there was a severe PHT (0.87 +/- 0.15 vs. 0.73 +/- 0.14, respectively, P = 0.02). The areas under the receiver operating characteristic curves for the diagnosis of severe PHT was 0.79 +/- 0.07, not different from that of platelets and Child-Pugh score., Conclusion: In patients with liver disease or cirrhosis, Fibrotest is correlated with the presence and degree of PHT. Other studies are needed to confirm these results, especially in non-decompensated cirrhotic patients.

The model for end-stage liver disease (MELD) is a widely accepted and objective scoring system for end-stage liver disease (ESLD) but has never been evaluated for Budd-Chiari syndrome (BCS). We investigated whether MELD can be used to predict survival in patients with BCS. Patients with BCS (n = 237) were obtained from a large international study. Patients with ESLD (n = 281) were used to compare the discriminative ability of MELD in BCS versus other chronic liver diseases. MELD and the Rotterdam BCS index, a recently developed prognostic index for BCS, were calculated with standard equations. Receiver operating characteristic curves and concordance statistics (c-statistics) were used to assess the models' ability to predict 1-year survival. The median MELD score was 12.5 (range = -7.4 to 43.4) for BCS and 11.3 (-3.0 to 49.5) for ESLD (P = 0.12). The c-statistic of MELD in BCS was 0.695 [95% confidence interval (CI) = 0.59-0.80], in contrast to 0.848 (95% CI = 0.80-0.90) in ESLD. Survival was significantly poorer in ESLD than in BCS (P < 0.001). The c-statistic of the Rotterdam BCS index was 0.760 (95% CI = 0.67-0.85). The correlation between MELD and the Rotterdam BCS index was 0.61, and most of the discrepancy existed in BCS patients with a high prevalence of ascites and encephalopathy and preserved liver function. The addition of ascites and encephalopathy to MELD improved the c-statistic to 0.751 (95% CI = 0.65-0.85). In conclusion, MELD showed a suboptimal discriminative ability to predict survival in BCS. This was explained by the highly variable degree of liver dysfunction and hence clinical outcome in BCS in contrast to ESLD.

During 2001, Clostridium difficile infection was observed in 23 patients hospitalized in a hepatology ward (attack rate, 0.9%). Since strain typing ruled out a clonal dissemination, we performed a case-control study. In addition to antibiotic use as a risk factor, the C. difficile infection rate was higher among patients with autoimmune hepatitis (P<.01).

The molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage hepatitis (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known of the changes in liver gene expression during the early stages of liver fibrosis associated with chronic HCV infection, that is, the transition from normal liver (NL) of uninfected patients to the first stage of liver fibrosis (F1-CH-C). To obtain insight into the molecular pathogenesis of F1-CH-C, we used real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to study the mRNA expression of 240 selected genes in liver tissue with F1-CH-C, in comparison with NL. The expression of 54 (22.5%) of the 240 genes was significantly different between F1-CH-C and NL; 46 genes were upregulated and 8 were downregulated in F1-CH-C. The most noteworthy changes in gene expression mainly affected the transcriptional network regulated by interferons (IFNs), including both IFN-alpha/beta-inducible genes (STAT1, STAT2, ISGF3G/IRF9, IFI27, G1P3, G1P2, OAS2, MX1) and IFN-gamma-inducible genes (CXCL9, CXCL10, CXCL11). Interesting, upregulation of IFN-alpha/beta-inducible genes (but not IFN-gamma-inducible genes) was independent of histological scores (grade and stage of fibrosis) and HCV characteristics (hepatic HCV mRNA levels and the HCV genotype), and was specific to HCV (as compared to hepatitis B virus (HBV)). Other genes dysregulated in F1-CH-C, albeit less markedly than IFN-alpha/beta- and IFN-gamma-inducible genes, were mainly involved in the activation of lymphocytes infiltrating the liver (IFNG, TNF, CXCL6, IL6, CCL8, CXCR3, CXCR4, CCR2), cell proliferation (p16/CDKN2A, MKI67, p14/ARF), extracellular matrix remodeling (MMP9, ITGA2), lymphangiogenesis (XLKD1/LYVE), oxidative stress (CYP2E1), and cytoskeleton microtubule organization (STMN2/SCG10). Thus, a limited number of signaling pathways, and particularly the transcriptional network regulated by interferons, are dysregulated in the first stage of HCV-induced liver fibrosis. Some of the genes identified here could form the basis for new approaches aimed at refining IFN-based therapies for chronic HCV infection.