Child-Pugh Status Research Articles

Renal failure and cirrhosis: A systematic review of mortality and prognosis

To evaluate renal failure (RF) in cirrhosis to determine and quantify its prognostic significance. Studies were identified by MEDLINE, EMBASE, Cochrane, ISI Web of Science (1977-2010); search terms included renal failure, mortality, and cirrhosis. Included studies (n=74) reported >10 patients and mortality data (8088 patients). Mortality at 1, 3, and 12 months was evaluated with respect to Child-Pugh score, serum creatinine, ascites, ICU status or sepsis, prospective study design, and publication year. Pooled odds ratio (POR) for death was compared for RF vs. non-RF (5668 patients). Overall median mortality for RF patients was 67%: 58% at 1 month and 63% (IQR 54-79) at 12 months. POR for death RF vs. non-RF patients was 7.6 (95%CI 5.4-10.8). Overall mortality before 2005 (1264 patients) was 74% and after 2005 (2833 patients) was 63% with a marked reduction only at 30 days (71% vs. 52%). This study provides a measure of the increased risk of death in cirrhosis with renal failure. RF increases mortality 7-fold, with 50% of patients dying within one month. Preventative strategies for RF are needed.

Clinical Outcomes of Lamivudine-Adefovir Therapy in Chronic Hepatitis B Cirrhosis

To determine the clinical outcome of chronic hepatitis B cirrhotics on antiviral therapy. The long-term outcome of hepatitis B cirrhotics on therapy remains to be characterized. A large clinic cohort of chronic hepatitis B cirrhotic patients were enrolled in a treatment program of lamivudine ± adefovir therapy. Patients were analyzed for clinical outcomes, and predictors of these outcomes were evaluated by multivariate analysis. Clinical outcomes of ascites, encephalopathy, hepatocellular carcinoma (HCC), and progression in Child-Pugh score, Model for End-stage Liver Disease score, and mortality were assessed. Data were analyzed by Kaplan-Meier graphs, log-rank test, and Cox regression. Of 143 chronic hepatitis B cirrhotics, 19.6% had decompensated cirrhosis. At 5 years, the mean survival was 83.6%, development of ascites, HCC, encephalopathy, and deterioration in Child-Pugh score were 7.0%, 15.9%, 10.8%, and 16.9%, respectively. The overall progression of liver-related complications was 32.8% at 5 years. Multivariate analysis showed that ascites, albumin ≤28 g/L, Child-Pugh score ≥7.9, Model for End-stage Liver Disease score ≥10.9 were significantly associated with liver-related complications. Low albumin and low hepatitis B virus DNA were independent factors for liver-associated mortality. Lamivudine resistance did not affect mortality or liver disease progression. When stratified by Child-Pugh status, the mean survival of those with Child C cirrhosis was worse than Child A and B cirrhosis (P<0.001, log-rank test). Early deaths (≤12 mo) were due to liver failure or sepsis, whereas deaths ≥12 mo were mainly due to HCC. Decompensated chronic hepatitis B cirrhotics may suffer early mortality despite antiviral treatment, and therefore should be considered for early liver transplantation.

Transarterial Chemoembolization Complicated by Deteriorating Hepatic Function

Worsening hepatic function is a well-known potential complication of chemoembolization and occurs in up to 58% of patients undergoing chemoembolization. Although liver function returns to baseline levels within 3-4 weeks in the majority of patients, fulminant liver failure and death occur with a reported frequency of ~2-10%. Poor performance status, portal vein obstruction, biliary obstruction, extensive tumor burden, and Child-Pugh status B or C are among factors predisposing to an increased risk of transient or fulminant hepatic failure, with Child-Pugh status being the most accurate. Unless the patient is a candidate for liver transplantation, treatment for hepatic failure is limited to supportive measures.

961 HEPATOCELLULAR CARCINOMA AND FERROPORTIN DISEASE

Aims: To evaluate epidemiology, clinical features and survival of HCV-related HCC in a wide time range in Italy. Methods: Multicenter retrospective study including 2750 patients prospectively recruited by the ITA.LI.CA group (11 units). The patients were classified in three groups (GA, HCV associated or not with other etiologies, GB, pure HCV, and GC, alternative etiologies) and sub-grouped in 5 time cohorts, of 5 years (1986–90, 91–95, 96– 2000, 2001–2005) but for the last one (2006–2008). The following features were analyzed: age, gender, Child–Pugh status, diagnosis for surveillance, stage, thrombosis and metastases, treatment and survival (Kaplan–Meier, Log-Rank). Results: 1793 patients were included in GA, 1440 in GB, 957 in GC. Both the number of GA and GB patients reached a peak in the 1996–2000 to then gradually drop, lowest values being observed in the last three years (p = 0.0001 GA, 0.01 GB). Mean age at diagnosis progressively increased in GA (p < 0.0001) and GB (p < 0.001) but not in GC. Same was true for the percentage of cases diagnosed under surveillance (GA p=0.019, GB p=0.0038) and for the share of patients in Child–Pugh A stage (GA p=0.01, GB p=0.0077). Mean tumor size decreased in all subgroups, tumor stage improved significantly only in GB. Median survival significantly increased in all groups but more significantly so in GA and GB, with a significant difference between GA and GB vs GC in the last 3 time periods (p = 0.02). Conclusions: The incidence of HCC in HCV-related liver disease is decreasing in Italy since 2001. HCV-related HCC patients are older, more frequently diagnosed under surveillance, more frequently characterized by conserved liver function and smaller tumors, with an earlier tumor stage when HCV is the only etiologic factor. Finally their survival dramatically improved in the last 15 years, to a larger extent than in patients with different etiology. We therefore expect a further drop in incidence and mortality for the disease in the years to come.

Single-institution experience using transarterial chemoembolization (TACE) with carboplatinum (carbo) and doxorubicin in patients (pts) with hepatocellular carcimona (HCC) awaiting liver transplantation (LTx).

336 Background: LTx is the best treatment option for multinodular HCC and those with advanced liver dysfunction. Tumor progression occurs in 20-50% of pts on liver transplant list. TACE is increasingly used as locoregional therapy and as a bridge to LTx. We report here our single institutional experience with TACE using carbo and doxorubicin in pts with HCC awaiting LTx. Methods: Retrospective chart review was performed in all pts who had TACE between 2008 and June 2010. Our institutional protocol uses a fixed dose of carbo 300mg, doxorubicin 50mg, in 10ml of lipoidol solution. We analyzed pt demographics, etiologies of liver disease, Child-Pugh status, CLIP scores, size of tumor, alpha-fetoprotein (AFP), toxicity, length of stay, and transplantation statistics. Results: 32 pts (28 men) were treated with 39 TACE procedures. The median age was 57 (32-83). 28 of 32 had cirrhosis with Child's A/B/C 36/51/18% respectively. The major etiologies of cirrhosis were hepatitis C (HCV) 8, alcohol and HCV 19, alcohol 7; portal vein thrombosis in 8 pts. The median tumor size was 6.2 cm (range 2-12 cm) and 81% were multifocal CLIP score 0,1/2,&gt;3 were 5/62/38%. There were no mortality within 30 days of TACE procedure. The majority of the pts were discharged after 24 hr observation; 6 pts require readmissions within 30days. There was no systemic hematologic toxicity. 11 pts had elevated AFP at baseline and 6/11 (54%) had &gt;50 % reduction in AFP value. 11pts (34%) received Ltx; 3 pts came off the LTx list due to disease progression, 2 pts are still on transplant list, and 16pts not able to be listed. 42% of pts received sorafenib in addition to TACE. The median time from last TACE to LTx was 55 days and 4 pts received transplantation within 30days. Very good pathological treatment effect was observed in 8/11 explanted liver. Conclusions: Our regimen of TACE with carbo/doxorubicin appears to be a safe and tolerable approach for localized treatment as a bridge to liver transplantation. It has acceptable toxicity and is associated with good AFP and pathological responses. We plan to evaluate different baseline parameters for better pt selection. No significant financial relationships to disclose.

T-5 Oncostatin M, overexpressed in hepatocellular carcinoma, up-regulates SERPIN-B3 expression in hepatic cancer cells

Background: In the western world HCV is the leading etiologic factor of HCC. Overall HCV impact on HCC-related mortality is increasing, but recent data from Italy suggest an initial drop. Aims: To evaluate epidemiology, clinical features and survival of HCV-related HCC in a wide time range in Italy. Methods: Multicenter retrospective study including 2769 patients prospectively recruited by the ITA.LI.CA group. The patients were classified in 3 groups (Group A [G.A.], HCV associated or not with other etiologies, Group B [G.B.], pure HCV, and Group C [G.C.], alternative etiologies) and sub-grouped in 5 years time cohorts (1986-90, 91-95, 96-2000, 2001-2005) but for the last one (2006-2008). Age, gender, Child-Pugh status, diagnosis for surveillance, stage, thrombosis and metastases, treatment and survival (Kaplan-Meier, Log-Rank) were analyzed. Results: 1780 patients were included in G.A., 1430 in G.B., 989 in G.C. The number of G.A. and G.B. patients reached a peak in the 1996-2000 to then gradually drop, lowest values being observed in the last three years (p=0.0001 G.A., 0.01 G.B.). Mean age at diagnosis progressively increased in G.A. (p<0.0001) and G.B. (p<0.001), but not in G.C, as did the percentage of cases diagnosed under surveillance (G.A. p=0.019, G.B. p=0.0038) and the share of patients in Child-Pugh A stage (G.A. p=0.01, G.B. p=0.007). Tumor size decreased in all subgroups, stage improved significantly only in G.B. Median survival significantly increased in all groups but more significantly in G.A. and G.B., with a significant difference among G.A. and G.B. vs G.C. in the last 3 time periods (p=0.02). Conclusions: The incidence of HCC in HCV-related liver disease is decreasing in Italy since 2001. HCV-related HCC patients are older, more frequently diagnosed under surveillance, more frequently characterized by conserved liver function and smaller tumors, with an earlier tumor stage when HCV is the only etiologic factor. Finally their survival dramatically improved in the last 15 years, more than in patients with different etiology. We therefore expect a further drop in incidence and mortality for the disease in Italy in the years to come.

Comparison between endoscopic sclerotherapy and band ligation for hemostasis of acute variceal bleeding

To compare band ligation (BL) with endoscopic sclerotherapy (SCL) in patients admitted to an emergency unit for esophageal variceal rupture. A prospective, randomized, single-center study without crossover was conducted. After endoscopic diagnosis of esophageal variceal rupture, patients were randomized into groups for SCL or BL treatment. Sclerotherapy was performed by ethanolamine oleate intravascular injection both above and below the rupture point, with a maximum volume of 20 mL. For BL patients, banding at the rupture point was attempted, followed by ligation of all variceal tissue of the distal esophagus. Primary outcomes for both groups were initial failure of bleeding control (5 d), early re-bleeding (5 d to 6 wk), and complications, including mortality. From May 2005 to May 2007, 100 patients with variceal bleeding were enrolled in the study: 50 SCL and 50 BL patients. No differences between groups were observed across gender, age, Child-Pugh status, presence of shock at admission, mean hemoglobin levels, and variceal size. No differences were found between groups for bleeding control, early re-bleeding rates, complications, or mortality. After 6 wk, 36 (80%) SCL and 33 (77%) EBL patients were alive and free of bleeding. A statistically significant association between Child-Pugh status and mortality was found, with 16% mortality in Child A and B patients and 84% mortality in Child C patients (P<0.001). Despite the limited number of patients included, our results suggest that SCL and BL are equally efficient for the control of acute variceal bleeding.

Undiluted N-butyl cyanoacrylate is safe and effective for gastric variceal bleeding

Gastric variceal bleeding is associated with significant morbidity and mortality in patients with portal hypertension. N-butyl cyanoacrylate (NBC), mixed with lipiodol, has been shown to be effective in controlling bleeding, but is associated with the risk of distal embolization. To study the efficacy and safety of undiluted NBC in the management of gastric varices (GV). Prospective cohort study. Single tertiary care center. 170 consecutive patients with GV. Standardized technique of undiluted NBC injection for management of GV. Achievement of initial hemostasis, rate of rebleeding, procedure-related complications, and mortality. GV were identified in 170 patients, 87 of whom were treated with 261 injections of undiluted NBC. Among 46 patients with active bleeding of GV, initial hemostasis was achieved in 84.8%. Rebleeding was seen in 23.4% patients over a mean follow-up of 16 months. No case of clinical distal embolization was seen. Large GV size, fundal location, and large esophageal variceal size were predictive of GV bleed. The mortality was 8.8% for all patients with GV; 10.3% for patients with GV treated with NBC, and 7.2% for those with GV not treated with NBC. Child-Pugh status was the only predictor of mortality. Only 1 intervention group. Undiluted NBC is safe and effective in the management of gastric variceal bleeding.

Management of ascites after radical surgery in gastric cancer patients with liver cirrhosis

Objective To evaluate the safety of radical lymph node dissection on gastric cancer patients with liver cirrhosis and management of ascites.Methods A radical lymph node dissection on 26 gastric cancer patients with liver cirrhosis(LC) were reviewed retrospectively.Results Child-Pugh status was grade A in all 26 patients,and a D2 lymph nodes dissection was performed in 25 (96.2% )patients.The mean number of dissected lymph nodes was 33 ± 11.An abdominal drain was placed in 12 (46.2% )patients,and the average amount of fluid drainage was 463 ml/d.The drainage tube was removed on about days,and diuretics were used in 8(30.8% )patients.Conclusion An extended lynph node dissection is safe in gastric cancer patients with mild LC.Liver cirrhosis and postoperative ascites can be managed conservatively without any complications. Key words: Gastric cancer; Liver cirrhosis; Ascites radical surgery

Minor versus major hepatic resection for small hepatocellular carcinoma (HCC) in cirrhotic patients: A 20-year experience

The choice between minor versus major resection or anatomic versus nonantatomic resection for small (<5 cm) solitary hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial. The aim of our study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) after minor or major hepatic resection for small solitary HCC in cirrhotic patients. Between January 1983 and December 2002, patients with solitary HCC of < or = 5 cm in size who had histologically proven liver cirrhosis and microscopically tumor-free margin were included. These selected patients underwent either minor (< or = 2 segments) or major (> or = 3 segments) hepatectomy. In 373 patients, 259 underwent minor and 114 underwent major hepatectomy. Patients in the minor resection group had more severe underlying liver disease (P = .005). Therefore, only 29.3% received anatomic resection in the minor resection group in comparison with 72.8% in the major hepatectomy group (P = .0001). No difference was found in postoperative morbidity (P = .105), mortality (P =.222), intrahepatic recurrence (P = .742), and 5-year DFS and OS (31.6% vs 31.8%, P = .932 and 50.7% vs 44.0%, P = .114) in both groups. The type of operative resection was not found to be a significant factor affecting survival in univariate analysis, but the preoperative liver function (alanine aminotransferase [AST] or alanine aminotransferase [ALT], serum albumin, or Child-Pugh status), tumor characteristics (alpha-feto protein, size, and presence of daughter nodules), and blood transfusion were found to be independent factors that affect the DFS and OS in a multivariate analysis. The severity of cirrhosis and tumor characteristics depicts long-term survival rather than the type of resection in HCC.

Risk Factors for Developing Ischemic-Type Biliary Lesions After Liver Transplantation

Ischemic-type biliary lesions (ITBL) account for a major part of patients' morbidity and mortality after orthotopic liver transplantation (OLT). The exact origin of this type of biliary complication remains unknown. This study retrospectively evaluated 1843 patients. Patients with primary sclerosing cholangitis were excluded from this study. The diagnosis of ITBL was established only when all other causes of destruction of the biliary tree were ruled out. Donor age (P = 0.028) and cold ischemic time (CIT) (P = 0.002) were found to be significant risk factors for the development of ITBL. Organs that were perfused with University of Wisconsin (UW) solution developed ITBL significantly more often than Histidine-Tryptophan-Ketoglutarate (HTK)-perfused organs (P = 0.036). The same applied to organs harvested externally and shipped to our center versus those that were procured locally by our harvest teams (P < 0.001). Pressure perfusion via the hepatic artery significantly reduced the risk of ITBL (P = 0.001). The only recipient factor that showed a significant influence was Child-Pugh score status C (P = 0.021). Immunologic factors had no significant impact on ITBL. The clinical consequences of this study for our institution have been the strict limitation of CIT to < 10 h and the exclusive use of HTK solution. We further advocate that all organ procurement teams perform pressure perfusion on harvested organs.

Prospective Randomized Study of Doxorubicin-Eluting-Bead Embolization in the Treatment of Hepatocellular Carcinoma: Results of the PRECISION V Study

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge—conventional TACE. Recently, a drug-eluting bead (DC Bead®) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

Intestinal Permeability in Cirrhotic Patients With and Without Spontaneous Bacterial Peritonitis: Is the Ring Closed?

Impaired intestinal permeability (IP) may have a role in the pathogenesis of ascites and in spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis (LC). The aim of this study was to assess IP in LC patients with respect to healthy controls. IP was evaluated by the (51)Cr-ethylenediaminetetraacetic acid ((51)Cr-EDTA) permeability test in 52 LC patients and in 48 sex- and age-matched controls. The presence of (51)Cr-EDTA was also evaluated in ascitic fluid after therapeutic paracentesis in all LC patients with ascites. An altered IP was found in 45% of LC patients compared with 4% of controls (P<0.00001). IP impairment was significantly associated with Child-Pugh status (75% of Child C patients vs. 39% of Child B and 22% of Child A patients), with the presence of ascites (60% in ascitic patients vs. 31% in nonascitic patients), and with a history of SBP (100% of patients with SBP vs. 50% of those without SBP). (51)Cr-EDTA was present in all ascitic samples obtained from patients with SBP compared with 22% of patients without SBP. IP derangement was a common finding in LC, especially in patients with more advanced disease (presence of ascites and history of SBP). The presence of (51)Cr-EDTA in ascites in patients with SBP suggests an altered permeability of splancnic vessels and/or peritoneal membranes. Further studies are required to assess (51)Cr-EDTA urine and ascite cutoffs to set up SBP preventive strategies.

Incidence of and risk factors for ischemic-type biliary lesions following orthotopic liver transplantation

Ischemic-type biliary lesions (ITBL) account for a major part of patients' morbidity and mortality after orthotopic liver transplantation (OLT). The exact origin of this type of biliary complication remains unknown. This study retrospectively evaluated 1843 patients. Patients with primary sclerosing cholangitis were excluded from this study. The diagnosis of ITBL was established only when all other causes of destruction of the biliary tree were ruled out. Donor age (P = 0.028) and cold ischemic time (CIT) (P = 0.002) were found to be significant risk factors for the development of ITBL. Organs that were perfused with University of Wisconsin (UW) solution developed ITBL significantly more often than Histidine-Tryptophan-Ketoglutarate (HTK)-perfused organs (P = 0.036). The same applied to organs harvested externally and shipped to our center versus those that were procured locally by our harvest teams (P < 0.001). Pressure perfusion via the hepatic artery significantly reduced the risk of ITBL (P = 0.001). The only recipient factor that showed a significant influence was Child-Pugh score status C (P = 0.021). Immunologic factors had no significant impact on ITBL. The clinical consequences of this study for our institution have been the strict limitation of CIT to <10 h and the exclusive use of HTK solution. We further advocate that all organ procurement teams perform pressure perfusion on harvested organs.

Phase II study of single agent perifosine in patients with hepatocellular carcinoma (HCC)

e15505 Background: Perifosine (Peri) is a novel oral alkylphospholipid with effects on multiple signal transduction pathways including Akt, MAPK and JNK. Unresectable HCC continues to have dismal prognosis. In a phase III randomized study, sorafenib demonstrated a 2% partial response (PR) rate with a median time to symptomatic progression of 4.1 months (mos) and radiologic progression of 5.5 mos, however patients (pts) had not received prior systemic treatment. Hence, additional therapies are needed. Peri was evaluated in a phase II multi-disease trial where 558 pts were randomized to daily vs. weekly schedules of Peri (50/100 mg daily or 900/1,200 mg weekly) with 42 of the pts having HCC. The following are the efficacy and safety results of this sub-group. Methods: Pts with advanced measurable HCC, up to 3 prior systemic treatments allowed. Normal organ / marrow function required. Primary outcome analyses included median time to progression (TTP) and disease control rate (DCR; CR+PR+SD &gt; 12 weeks). Results: Of the 42 HCC pts treated, the median age was 71 (range 26–83), 22 were male and 48% had received &gt; 1 prior systemic therapy. Child-Pugh status not available. As of 12/08, 32/42 pts were evaluable for efficacy (5 withdrew consent &lt; 30 days, 4 toxicity &lt; 30 days, 1 lost to follow up). One patient achieved a PR (3%) and 15 (47%) had stable disease &gt; 12 weeks; overall DCR of 50%. Median TTP was 14 wks (range 2–86). As of 12/08, one patient remains active at 12 mos. The daily dose was well tolerated. The weekly dose was significantly more toxic (3 of the 4 who came off treatment &lt; 30 days due to toxicity were on weekly). Most common grade 1/2 toxicities were GI related and fatigue. Grade 3/4 drug-related toxicities &gt; 10% included: abdominal pain (12%), elevated liver enzymes (10%) and fatigue (10%). Conclusions: Perifosine was well tolerated at the daily dose and overall demonstrates clinical benefit in patients with advanced HCC as reflected by an encouraging TTP. A combination study with sorafenib is ongoing and future randomized studies are under consideration. [Table: see text]

A randomized phase II trial of a drug eluting bead in the treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization

4523 Background: Transcatheter arterial chemoembolization (TACE) has been shown to offer a survival benefit for patients with intermediate-stage hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes the administration of a doxorubicin-in-oil emulsion followed by gelatine sponge particles. Recently, a drug-eluting bead (DEB) has been developed to enhance drug delivery to the tumor and reduce its systemic availability. Purpose of this randomized trial was to compare conventional TACE with DEB-TACE for the treatment of intermediate-stage HCC in patients with cirrhosis. Methods: Two hundred and twelve patients (185 males and 27 females; mean age, 67 years) with Child-Pugh A or B liver cirrhosis and large and/or multinodular, unresectable HCC were randomized to receive DEB-TACE (DC Bead; Biocompatibles, UK) uploaded with doxorubicin or conventional TACE with doxorubicin, lipiodol, and gelatin sponge particles. Randomization was stratified according to Child Pugh status (A or B), performance status (ECOG 0 or 1), bilobar disease (yes or no) and prior curative treatment (yes or no). Tumor response at 6 months was the primary study endpoint. An independent, blinded review of magnetic resonance imaging studies was conducted to assess tumor response according to amended RECIST criteria. Results: DEB-TACE with doxorubicin showed a higher rate of complete response, objective response and disease control compared with conventional TACE (27% vs 22%; 52% vs 44%; and 63% vs 52%, respectively; p&gt;0.05). Patients with Child Pugh B, ECOG 1, bilobar disease and recurrence following curative treatment showed a significant increase in objective response (p=0.038) compared to the control. There was a marked reduction in serious liver toxicity in patients treated with DEB-TACE. The rate of doxorubicin related side effects was significantly lower (p=0.0001) in the DEB-TACE group compared with the conventional TACE group. Conclusions: DEB-TACE with doxorubicin is safe and effective in the treatment of intermediate-stage HCC and may offer benefit to patients with more advanced disease. No significant financial relationships to disclose.

Esophageal variceal pressure is a major predictor of variceal bleeding in cirrhotic patients

Objective To prospectively study the main risk factors of variceal bleeding in cirrhotic patients. Methods Fifty-seven patients with liver cirrhosis and esophageal varices who had never experienced variceal bleeding were followed up for 12 months. The patients underwent measurements of esophageal variceal pressure by non-invasive endoscopic balloon technique. The endpoint of the study was the presence of a variceal hemorrhage. The relationship between variceal hemorrhage and endoscopic findings including varices, variceal pressure, Child-Pugh status, ascites, and etiology of cirrhosis was studied. Results Thirty-four patients (59.6% ) developed a variceal hemorrhage. In univariate analysis, the level of variceal pressure (P= 0. 001), the size of varices (P=0. 006), and the endoscopic red color sign on the variceal wall (P=0. 012) predicted higher risks of variceal hemorrhage. The multiple logistic regression revealed that variceal pressure was a major predictor of the risk for a first variceal bleeding (OR=2. 817, P=0. 003). The area under the receiver operating characteristic (ROC) of variceal pressure for predicting variceal bleeding was 0. 98, and the variceal pressure cutoff value was 25.3 mm Hg (1 mm Hg=0. 133 kPa) with both specificity and sensitivity of 91 %. Conclusion The level of variceal pressure is a major predictor for variceal bleeding in cirrhotic patients. Key words: Esophageal and gastric varices; Liver cirrhosis; Portal pressure

Interest of BIS monitoring to guide propofol infusion during the anhepatic phase of orthotopic liver transplantation

The anhepatic phase of orthotopic liver transplantation (OLT) is associated with significant changes in pharmacokinetics. The aim of this study was to compare the influence of this phase on propofol target concentrations during BIS guided target controlled infusion (TCI). Prospective study. Eight patients aged 25 to 65 years, Child-Pugh status A-B scheduled for OLT were prospectively included. Anesthesia was performed using TCI of propofol (Diprifusor, Marsh pharmacokinetic model), sufentanil and cisatracurium. Propofol target concentration was adjusted to maintain BIS values between 40 and 50. To maintain stable BIS values, propofol target concentrations should be decreased during the anhepatic phase versus the dissection one (2.0 microg/ml+/-0.8 versus 3.0 microg/ml+/-0.9, p<0.0001). BIS could be useful to titrate propofol infusion during the anhepatic phase of OLT.

Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome

Hepatocellular carcinoma (HCC) is uncommon in young adults. This study examined the clinical characteristics and survival outcome of young HCC patients compared with those in older patients. Data were prospectively collected from 638 patients diagnosed with HCC over a 9-year period. Patients aged < or =40 years at diagnosis of HCC were defined as young HCC patients. Their clinical characteristics and survival was compared with those aged >40 years. The prevalence of young HCC was 8.6% (55/638). Young HCC patients had a significantly higher rate of hepatitis B-related disease (HBsAg positivity: 85.5% vs. 59.7%, P = 0.003), better Child-Pugh status (Child-Pugh class A: 69.1% vs. 43.9%, P = 0.002), and lower rates of cirrhosis (12.7% vs. 34.3%, P = 0.001) compared with the older group. They had more advanced disease at diagnosis, with higher alpha-fetoprotein levels (>12 000 microg/l: 45.4% vs. 30.5%, P = 0.026), a higher incidence of portal vein involvement (63.6% vs. 40%, P = 0.003), and a more advanced TNM stage (TNM IV: 83.6% vs. 66.4%, P = 0.018). More young patients were eligible for surgical resection (18.2% vs. 8.2%, P = 0.014). The overall survival between the two groups was similar, but when the patients were stratified for stage of disease, the median survival of young patients with early disease was superior to that of older patients (51.2 vs. 11.6 months, P = 0.025). HCC in young adults occurs mainly in hepatitis B carriers and is often diagnosed at an advanced stage. Their survival outcome is not different from that of older patients because the advanced disease at presentation offsets the advantages of better liver function and a higher resection rate. However, there is a distinct survival advantage for young patients diagnosed with early disease. These results support the importance of extending HCC surveillance to young hepatitis B carriers.

Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma and vascular invasion or extrahepatic spread: A subanalysis from the SHARP trial

4584 Background: Liver cancer is the third leading cause of cancer death globally, with most deaths occurring within one year of diagnosis. The multi-kinase inhibitor sorafenib became the first treatment approved by the FDA and EMEA for the treatment of HCC based on data from the phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) trial, which demonstrated that sorafenib 400mg bid increased overall survival (OS) vs placebo in patients with advanced HCC. The influence of risk factors such as macroscopic vascular invasion (MVI) and/or extrahepatic spread (EHS), on the safety and efficacy of sorafenib has not previously been reported. Here we compare sorafenib versus placebo in patients with and without MVI and/or EHS. Methods: Patients with advanced, measurable HCC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2 and Child-Pugh status A received either sorafenib (400mg bid) or placebo. Endpoints included OS, time to progression (TTP; based on independent tumor assessment), and...