yr)* Age started (yr)* >0 30 (23-36) 17 (16-18)+ 30 (23-36) 16 (15-18) >40 20 (14-27) 22 (18-30)+ 22 (16-30) 19 (17-25) >80 12 (6-19) 29 (21-38)+ 13 (7-22) 25 (18-33) >120 3 (0-12) 32 (24-41)++ 4 (0-10) 28 (21-37) >160 0 (0-7) 33 (27-41)+++ 0 (0-7) 30 (24-39) *: median (interquartile range).+: p < 0.001, ++: p = 0.02, +++: p = 0.017 by Mann-Whitney test for patients vs controls.

Summary Serum levels and liver expression of CCL2 are increased in patients with alcoholic hepatitis (AH). In an experimental model of alcoholic liver disease (ALD), CCL2 was implicated in proinflammatory cytokines activation and hepatic lipid metabolism, but its role in human disease is currently unknown. In a large cohort of ALD patients, we analysed plasma levels and liver expression of CCL2 and their association with liver disease severity and histological lesions. We also studied the relationship between −2518 A > G CCL2 and CCR2 190 A/G polymorphisms and severity of ALD. We show that CCL2 plasma levels are increased in ALD patients compared with healthy subjects. AH patients had significantly higher plasma levels and hepatic expression of CCL2 than patients without AH. Plasma levels and hepatic expression of CCL2 were associated with disease severity. CCL2 liver expression was correlated with neutrophil infiltrate and interleukin (IL)-8 expression, but not with steatosis. Moreover, there were more G-allele carriers of −2518 A > G CCL2 polymorphism in severe AH patients than in other ALD patients. Our results demonstrate that CCL2 is increased in ALD, particularly in severe forms, and suggest a role for CCL2 in the pathogenesis of ALD via neutrophil recruitment.

The treatment of hepatocellular carcinoma (HCC) in cirrhotic patients is challenging: the incidence is increasing, the cirrhosis dramatically limits the tolerance to treatment possibilities, there are many therapeutic modalities but resources are limited, namely in the context of organ shortage for transplantation. Liver transplantation (LT) is the optimal treatment as it combines the largest tumor resection possible and the correction of the underlying liver disease. Due to organ shortage however, LT is reserved for early-stages HCC. Surgical resection and radiofrequency destruction represent potentially curative options in highly selected patients. Arterial embolizations, chemo- or radio-embolizations, allow local tumor control but are not curative. These techniques could be performed before surgical resection or LT, to downstage the tumor and/or to control tumor progression while waiting for a graft. Finally, sorafenib is the only systemic treatment which has shown a survival benefit in advanced HCC. The benefit of combination of sorafenib and surgical treatments remains undetermined. The challenge in the management of HCC in cirrhotic patients is to integrate both individual (age, comorbidities, cirrhosis stage, tumor stage, specific contraindications to LT, etc.) and collective variables (expected waiting time before LT) to determine the best therapeutic option for each patient. In this process, multidisciplinarity is a key for success.

ABSTRACT HCV core antigen (Ag) and HCV RNA levels were evaluated in matched liver biopsy samples and sera from 22 patients with hepatitis C infection by using the quantitative Architect HCV Ag immunoassay and a real-time RT-qPCR assay, respectively. The data showed a strong correlation between liver and serum compartments of HCV Ag levels (r = 0.80) and HCV RNA levels (r = 0.87). In summary, the serum HCV Ag and RNA levels reflect the intrahepatic values.

Several surgical techniques have been developed to allow liver transplantation in cases of complete portal vein thrombosis in the recipient. Despite this, these transplantations remain associated with a significant complication rate. We report herein a case of liver transplantation in a patient with complete portal vein thrombosis, underlying the potential pitfalls and the risk of intestinal sutures in case of hepaticojejunostomy. We discuss the technical options and their relative indications in such cases.

Background and Aims: Insulin resistance (IR) plays an important role in various chronic liver diseases.In alcoholic liver disease (ALD), BMI and blood glucose have been identified as risk factors for fibrosis.However, the impact of IR in ALD is currently unknown.The aim of our study was to evaluate the relationship between IR and histological damage, portal hypertension and severity of liver disease in ALD.Patients and Methods: From April 2009 to September 2010, 103 consecutive patients with excessive alcohol intake (>40 g/day) undergoing transjugular liver biopsy for suspected liver disease were included in the study.IR was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR).Patients with a history of diabetes or other cause of liver disease were excluded.Results: 103 patients (64% males, mean age 53.45±9.79years, mean BMI 25.41±5.38kg/m 2 , 69% with cirrhosis, 12% died within 6 months 40% had histological alcoholic hepatitis [AH], median MELD score 12.09 [7.99-20.18],median hepatic venous pressure gradient [HPVG] 13 [6-18] mmHg, median HOMA-IR 2.76 [1.33-5.29])were included with a median follow-up of 3 months.HOMA-IR showed a significant correlation with HVPG (r = 0.29 p = 0.004), BMI (r = 0.37, p < 0.001), INR (r = 0.20, p = 0.049) and platelets (r = -0.43,p < 0.001).Conversely, HOMA-IR was not correlated with steatosis, the presence and severity of AH or with the MELD score.A ROC curve analysis (AUC = 0.67, p = 0.005) showed that the optimal HOMA-IR cut-off to identify patients at risk of cirrhosis was 2.69 (sensitivity = 0.60, specificity = 0.69, positive and negative predictive value were 0.81 and 0.44 respectively).After adjustment for age, gender, BMI and presence of AH, HOMA-IR above 2.69 remained an independent predictor of cirrhosis (OR = 3.43, 95% CI = 1.97-10.96,p = 0.038).Moreover, this threshold was associated to a higher risk of 6 months' mortality (p = 0.043).Conclusions: In ALD, IR is correlated with the severity of portal hypertension.Furthermore, IR predicts 6 months' mortality and is independently associated to cirrhosis.IR may represent both a new predictor of severity and a new therapeutic target in ALD.

Conclusions:1.This group of compensated liver cirrhosis did not present increased IP, increased endotoxaemia, or altered duodenal histology.2. Presence of portal hypertension was not related to increased IP. 3. Cirrhotics presented higher levels of circulating interleukins, not explained by increased IP or by increased endotoxaemia.

BACKGROUND:Due to the organ shortage, marginal donors are increasingly used in liver transplantation (OLT). These grafts may be safely used in less critical recipients but, the real influence of extended donor criteria (EDC) remains uncertain when graft-recipient matching is not applied. Our study analyzed the impact of EDC on initial graft function within the Eurotransplant patient-driven allocation system.PATIENTS AND METHODS:We reviewed 70 OLT performed between 2004 and 2006. The impact of the following EDC were analyzed: age > 60; intensive care unit (ICU) stay > 4 days; peak serum Na(+) > 160 mEq/L; body mass index (BMI) > 30; cardiac arrest with cardiopulmonary resuscitation, and high doses of vasopressors. Early graft function, as defined according to peak transaminase level and spontaneous prothrombin time within the first 5 posttransplant days, was compared between the donors with none or one criterion (group A = 39) and those with >1 criterion (group B = 31).RESULTS:The most frequent EDC were high vasopressor use, ICU stay > 4 days and BMI > 30, were present in respectively 44%, 27%, and 16% of the donors. No EDC were present in 13 donors, one in 26, three in eight, and four in three. Demographics and origin and severity of the liver disease were similar in both groups. We failed to observe significant differences in initial graft function.CONCLUSION:The presence of EDC did not significantly affect early graft function in a population where donor and recipient were not matched. While this observation must be confirmed in a multicenter analysis, it tends to support the use of marginal liver grafts, even in patient-driven allocation systems.

The MELD score has now been implemented in the United States for liver allocation, but it has not been validated in Europe. Its association with posttransplant outcome is unclear. Optimal cutoff values of MELD and Child-Pugh scores to predict death on the liver waiting list were defined in a series of 137 cirrhotic patients listed for liver transplantation. Six-month actuarial survival while on the waiting list was 90% with a Child-Pugh <11 and MELD <17, whereas it decreased progressively to 40% at 6 months after listing for those having a Child-Pugh and MELD score >10 and >16. Analysis of a series of 112 patients (85 chronic liver disease and 27 hepatocellular carcinoma) revealed no change in MELD value at the time of transplantation compared to the score at the time of listing (mean +/- SD: 15.5 +/- 7.7 vs 15 +/- 5.8) with a mean waiting time of 118 days. Using either the optimal cutoff for MELD score (<17 or >16) or seven different strata (3 to 7, 8 to 10, 11 to 13, 14 to 16, 17 to 19, 20 to 22, 23 to 39), whether measured at listing or just before liver transplantation, there was no significant difference (chi(2) 4.97, P = .58) in survival: 82.7% and 63% at 6 and 60 months, overall. Our data confirm that the MELD score with only three parameters is as good as the Child-Pugh score to predict mortality on the Eurotransplant waiting list. The optimal cutoff to assess higher priority for the bad category is >16. There was no negative impact on short- or long-term prognosis of the bad categories of MELD.