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Objective: In alcoholic hepatitis (AH), development of targeted therapies is crucial and requires improved knowledge of cellular and molecular drivers in liver dysfunction. The unique opportunity of using explanted livers from patients with AH having undergone salvage liver transplantation allowed to perform more in-depth molecular translational studies., Design: We studied liver explants from patients with AH submitted to salvage transplantation (n=16), from patients with alcoholic cirrhosis without AH (n=12) and fragments of normal livers (n=16). Hepatic cytokine content was quantified. Hepatocyte function and proliferation and the presence of hepatic progenitor cells (HPCs) were evaluated by immunohistochemistry, western blot or quantitative PCR. Mitochondrial morphology was evaluated by electron microscopy., Results: Livers from patients with AH showed decreased cytokine levels involved in liver regeneration (tumour necrosis factor α and interleukin-6), as well as a virtual absence of markers of hepatocyte proliferation compared with alcoholic cirrhosis and normal livers. Electron microscopy revealed obvious mitochondrial abnormalities in AH hepatocytes. Importantly, livers from patients with AH showed substantial accumulation of HPCs that, unexpectedly, differentiate only into biliary cells. AH livers predominantly express laminin (extracellular matrix protein favouring cholangiocyte differentiation); consequently, HPC expansion is inefficient at yielding mature hepatocytes., Conclusions: AH not responding to medical therapy is associated with lack of expression of cytokines involved in liver regeneration and profound mitochondrial damage along with lack of proliferative hepatocytes. Expansion of HPCs is inefficient to yield mature hepatocytes. Manoeuvres aimed at promoting differentiation of HPCs into mature hepatocytes should be tested in AH., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Standardised measurement of remnant liver volume (RLV), where total liver volume (TLV) is calculated from patients' body surface area (RLV-sTLV), has been advocated. Extrapolating the model of living donor liver transplantation, we showed in a pilot study that the simplified RLV/body weight ratio (RLVBWR) was accurate in assessing the functional limit of hepatectomy. The aim of the study was to compare in a prospective series of extended right hepatectomy the predictive value of the RLVBWR and the RLV-sTLV at a cut-off of 0.5% (RLVBWR0.5%) and 20% (RLV-sTLV20%), respectively., Methods: We studied the impact of RLVBWR0.5% and of RLV-sTLV20% on three months morbidity and mortality in 74 non-cirrhotic patients operated on for malignant tumours. Of these, 47 patients who were not included in the initial pilot study were enrolled in a prospective validation cohort to reappraise the predictive value of each method., Results: RLVBWR and RLV-sTLV were highly correlated (Pearson correlation coefficient, 0.966). Three months overall and severe morbidity (grade 3b-5) and mortality were significantly increased in groups RLVBWR ≤ 0.5% and RLV-sTLVs ≤ 20% compared to groups >0.5% and >20%, respectively. The sensitivity and specificity in predicting death from liver failure were 100 and 84.1% for RLVBWR0.5% and 60 and 94.2% for RLV-sTLV20%, respectively. Similar results were observed in the validation cohort for the RLVBWR0.5% (lack of statistical power for RLV-sTLV as only 2 patients showed a RLV-sTLV ≤ 20%)., Conclusions: The RLVBWR0.5% is a method of assessing the remnant liver that is simple and as reliable as the standardised RLV-sTLV20%.

Background: Hepatocellular carcinoma in noncirrhotic liver (NC-HCC) presents usually with large size, which is seen as a contraindication to liver transplantation (LT) or even resection. The objective of our single-center study was to identify prognostic factors following resection of large NC-HCCs and to subsequently devise a treatment strategy (including LT) in selected patients., Methods: From 2000 to 2010, 89 patients who had hepatic resection for NC-HCC (large ≥ 8 cm in 52) were analyzed with regard to pathological findings, postoperative and long-term outcome., Results: Five patients died postoperatively. After a mean follow-up of 35 ± 30 months, NC-HCC recurred in 36 patients (26/47 survivors in group 8 cm+, 10/37 in group 8 cm-; p = 0.007). Five-year overall (OS) and disease-free survival (DFS) rates were significantly worse for group 8 cm+ (43.4% vs. 89.2% and 39.3% vs. 60.7% for group 8 cm-, p < 0.05). Seven patients underwent re-hepatectomy and/or LT for isolated intrahepatic recurrence, with 5-year DFS of 57.1%. In a multivariate analysis, the factors associated with poor OS and DFS were vascular invasion and tumor size ≥ 8 cm in the overall population and vascular invasion, fibrosis and satellite nodules in group 8 cm+. Adjuvant transarterial chemotherapy was a protective factor in group 8 cm+. In 22 isolated NC-HCC cases with no vascular invasion or fibrosis, tumor size had no impact on five-year DFS (85%)., Conclusions: Although patients with NC-HCC ≥ 8 cm had a poorer prognosis, the absence of vascular invasion or fibrosis was associated with excellent survival, regardless of the tumor size. In recurrent patients, aggressive treatment (including LT) can be considered., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background/aims: Management of post-cholecystectomy bile duct injuries may, in certain cases, require hepatectomy. In the literature, indications for hepatectomy in this setting are not clear., Methodology: A retrospective review of our database for patients referred for post-cholecystectomy bile duct injuries from January 2003 to January 2008 was performed., Results: We present three cases of hepatectomy among 45 patients (6.7%) referred for post-cholecystectomy bile duct injuries. Two of these patients had been referred after one or more previous attempts at operative repair in an outside hospital. In one patient, the decision to perform hepatectomy was based on the proximal pattern of biliary stricture aggravated by disruption of the right hepatic artery, leading to irreversible secondary sclerosing cholangitis. Biliary stricture also involved bifurcation and was complicated by liver atrophy in the 2 other patients. Despite complication(s) in 2 out of 3 patients, the long-term outcome was good in all cases., Conclusions: In our experience, the indication for hepatectomy in post-cholecystectomy bile duct injuries, combined with vascular injuries and liver atrophy in symptomatic patients.

Background: Right hepatectomy (RH) is the most common type of major hepatectomy and can be achieved without portal triad clamping (PTC) in non-cirrhotic liver. The present study reviews our standardized policy of performing RH without systematic PTC., Methods: One hundred and eighty-one consecutive RH were performed in non-cirrhotic patients, with division of the right afferent and efferent blood vessels prior to transection, without systematically using PTC. Prospectively collected data were analysed, focusing on the following endpoints: need for salvage PTC, ischaemic time, blood loss and post-operative outcome., Results: Extra-hepatic division of the right hepatic vessels was feasible in all patients, but was ineffective in 48 patients (26.5%) who required salvage PTC during transection. In those patients, the median ischaemic time was 20 min. The median blood loss was 500 ml (50-3000). Six patients (3.3%) experienced post-operative liver failure. Overall morbidity, severe morbidity and mortality were 42%, 12.1% and 1.6%, respectively, with peri-operative transfusion rate (16.6%) being the only factor associated with morbidity., Discussion: By performing RH with extra-hepatic vascular division prior to transection, PTC can be safely avoided in the majority of patients., (© 2012 International Hepato-Pancreato-Biliary Association.)

Objective: The use of ultrasonography is widespread for both the diagnosis and treatment of liver tumors. However, the measurement of liver volume by ultrasonography is not commonly done. We report an original method of liver volumetry using ultrasonography and an investigation into the usefulness of ultrasonography in this context., Methods: The data for 50 patients undergoing various types of major hepatectomy were collected. We preoperatively measured liver volume using ultrasonography, dividing the liver into three main compartments according to precise anatomical landmarks, and then made comparisons with the volume of the actual specimen after hepatectomy, for all of the study participants., Results: Total volume correlation between the two groups was good (r = 0.916, P < 0.001). However, the correlation was weaker in cases of right hepatectomy compared with other types of hepatectomy., Conclusion: This study demonstrates the possibility of doing liver volumetry using an ultrasound device. Further investigation to establish the reliability of this easily available and noninvasive approach is needed.

Background: The clinical development of liver-support devices based on perfusion of either pig hepatocytes cartridges or whole pig livers has been hampered by the ability to use sufficient liver cell mass to provide adequate metabolic support, limited perfusion times, and the potential for patient exposure to pig zoonotic diseases., Methods: We designed an original system in which an isolated intact pig liver was perfused extracorporeally under physiological conditions in a closed loop circuit with allogeneic pig blood and constant monitoring of major physiological and functional parameters. The perfusion circuit further included an interface membrane to provide for separation of patient and liver perfusion circulation., Results: Prolonged (6-21 hr) liver perfusion did not produce significant liver damage as reflected by modest rises in the levels of the serum transaminases, stability of main biochemical parameters (including potassium), and the maintenance of normal cellular morphology. Optimal liver function was documented as measured by lactate consumption, control of glycemia, and the results of clotting studies and functional assays. The perfused liver cleared 82% and 79% of peak bilirubin and ammonia concentrations with clearing kinetics identical throughout perfusion. Indocyanine green clearance was identical to that observed in the living donor before explant surgery., Conclusions: In conclusion, the extracorporeal pig liver perfusion apparatus described here allows optimal pig liver function for prolonged periods of time. The microporous membrane to provide separation of donor organ and recipient and the high level of functional activity suggest that this form of liver metabolic support may have important clinical applications.