DDW 2007:  Sunday Abstracts:


Topic:  Liver Transplantation - General

2. Use of hepatitis C-infected donors in liver transplantation: a case-control study

P. Kwo; S. Wilson; R. S. Mangus; A. Tector; J. A. Fridell; R. Vianna; S. Liangpunsakul; V. Misra; S. Bhardwaj



Hepatitis C is the major reason for the increase in HCC (Liver Cancer) the need for liver transplantation in the United States.  To meet the increasing demand for cadaveric donor livers, some centers transplant livers from hepatitis C (HCV)-infected donors into recipients with HCV-related cirrhosis. This study utilizes a case-control design to compare transplant outcomes for 38 recipients of livers from HCV-infected donors to those for 76 standard, non-extended criteria (ECD) donors (1 case / 2 controls) between 2001 – 2006.


Data was extracted from the transplant center registry, UNOS data, and from the original on-site donor data chart. Thirty percent of all donors met non-ECD criteria (standard donors) and were included as potential matches for the case-control study. Each HCV-positive liver donor recipient was matched to two standard donor recipients as matched standard donor controls (MSDC) by: recipient age +/- 10 years, primary diagnosis, cancer stage for those with HCC, recipient MELD +/- 5, and donor age +/- 10 years. Outcomes included graft and patient survival at 3-months, 1-year and 2-years; perioperative death; and, HCV recurrence by 4-month and 1-year fibrosis (F0-F4-Metavir).



The HCV-donor and matched standard donor control groups did not differ for recipient or donor demographics or in cold and warm ischemia (decrease in the blood supply) time. Survival results and fibrosis progression are shown in the table. Median follow- up time was 36 months. Kaplan-Meier actuarial survival demonstrated improved graft survival for HCV-infected donors with a trend toward significance (p=0.10).



These preliminary results suggest that HCV-infected liver transplant recipients receiving livers from HCV-infected donors may have a slower rate of fibrosis progression at 1-year. A trend was seen in survival advantage for those receiving HCV-donor grafts compared to standard donor controls. The use of HCV positive donors may be considered as a first line therapy to increase the available donor pool of organs in those undergoing liver transplantation for HCV-related cirrhosis.



Topic:  Liver Transplantation – Recurrence

218  Recurrent Hepatitis C After Liver Transplantation: On-Treatment Prediction Of Response To Peginterferon Alpha-2a/Ribavirin (Peg/Rbv) Therapy

I. Hanouneh; C. M. Miller; F. Aucejo; M. Quinn; N. N. Zein



Despite significant progress in the treatment of hepatitis C (HCV), sustained virologic response (SVR) in liver transplant recipients remains suboptimal and the clinical utility of SVR predictors during therapy is unknown.



Our Aims were to assess efficacy of peginterferon and ribavirin combination therapy (Peg/RBV) in liver transplant recipients and to estimate the predictive value of rapid virological responses (RVR, week 4) and early virological responses (EVR, week 12) in this population.



Retrospective analysis of prospectively collected data from all patients who were treated with Peg/RBV using a standardized protocol [28 patients (24 genotype 1 and 4 genotypes 2/3]. According to the protocol, all patients received 48 weeks of therapy independent of virologic response. Intention-to-treat analysis was used to measure the primary outcome (SVR). On-treatment predictors of response were defined as HCV RNA negative or > 2 log10 decrease from pretreatment baseline at 4 weeks (RVR) and 12 weeks (EVR).



SVR was seen in 9/28 (32%) patients. Patients infected with genotype 2/3 were more likely to achieve SVR than patients with genotype 1 [4/4 (100%) versus 5/24 (21%) p=0.006]. The highest rate of SVR was seen in patients with RVR (Specificity and Positive Predictive Value = 100%) while the highest rate of treatment failure was seen in those who did not have EVR (sensitivity and Negative Predictive Value = 100%, table). The negative predictive value of RVR to identify those who did not achieve SVR was also very high in this population (92%). EVR had low specificity (58%) and low positive predictive value (53%) to identify those with SVR. None of those with detectable HCV RNA at week 24 had SVR while 3/12 (25%) patients who were HCV RNA negative at week 24 did not have SVR due to breakthrough (1 patient) or relapse (2 patients).



1.     Peg/RBV is effective in the treatment of post-liver transplant recurrent HCV.

2.     On-treatment virologic monitoring is highly predictive of SVR and may optimize the virologic response and minimize toxicity.

3.     Given its high Positive and Negative Predictive Values, RVR appears to be the most appropriate decision time point for continuation of therapy.






Positive Predictive Value

Negative Predictive Value

week 4






95% CI


35.9, 99.6


71.5, 100


47.8, 100


61.5, 99.8

week 12






95% CI


66.3, 100


33.5, 79.7


27.8, 77


71.5, 100

Week 24






95% CI


66.3, 100


58.6, 96.4


42.8, 94.5


78.2, 100











Topic:  Current Treatment - Pegasys


4. Increased SVR Rate with 48 Wks’ Treatment and Higher RBV Dose in HCV Genotype 2/3 Pts Without a Rapid Virologic Response (RVR) Treated with Peginterferon Alfa-2a (40KD) (PEGASYS®) Plus RBV (COPEGUS®)

B. Willems; S. J. Hadziyannis; T. R. Morgan; M. Diago; P. Marcellin; D. E. Bernstein; P. J. Pockros; A. LinM. L. Shiffman; S. Zeuzem



ACCELERATE, a large-scale (n=1469) prospective study recently showed that, overall, peginterferon alfa-2a (40KD) plus ribavirin (RBV) for 24wks was superior to 16wks in hepatitis C virus (HCV) genotype 2/3 pts (EASL 2006:A734). In this study, two-thirds of pts achieved a rapid virologic response (RVR; HCV-RNA <50IU/mL at wk 4). These early-responder pts had a >80% probability of achieving an SVR with 16wks of therapy, suggesting that this shortened treatment regimen may be a reasonable customized option for RVR pts who cannot tolerate a full course of therapy. Conversely, pts without an RVR had an SVR rate of only 49% with 24wks’ treatment, suggesting that these pts may benefit from more intensive treatment regimens. To determine whether an intensified regimen of peginterferon alfa-2a plus RBV may be beneficial in genotype 2/3 pts without an RVR, we retrospectively examined available data from other pivotal clinical studies.



SVR and relapse rates following peginterferon alfa-2a (PEGASYS®) plus RBV (COPEGUS®) were analyzed in HCV genotype 2/3 pts who did not achieve RVR in two studies (NV15942, NV15801).   In NV15942 (Hadziyannis. Ann Int Med 2004), pts were randomized to 24 or 48wks of peginterferon alfa-2a 180µg/wk plus RBV 800 or 1000/1200mg/d. In NV15801 (Fried. NEJM 2002), pts received 48wks of peginterferon alfa-2a plus RBV 1000/1200mg/d.



·        RVR was achieved by a high proportion of genotype 2/3 pts (74% and 58% in NV15942 and NV15801).

·        In pts in NV15942 who did not achieve an RVR, the lowest relapse rate and the highest SVR rate (76%) was achieved with 48wks of peginterferon alfa-2a plus RBV 1000/1200mg/d (Table).

·        This compared with 61% for 48wks’ peginterferon alfa-2a plus RBV 1000/1200mg/d in NV15801 and 49% for 24wks’ peginterferon alfa-2a plus RBV 800mg/d in ACCELERATE.



Genotype 2/3 pts who do not achieve an RVR could receive added benefit if treated for 48wks with a higher dose of RBV (1000/1200mg/d).These results merit further investigation in a prospective controlled study to fully elucidate how treatment customization can benefit pts before formal recommendations can be made.


NV15942 ITT analysis

Peg-IFNα-2a + RBV 800mg/d

Peg-IFNα-2a + RBV 1000/1200mg/d

Peg-IFNα-2a + RBV 800mg/d

Peg-IFNα-2a + RBV 1000/1200mg/d

SVR, n/N (%) [95% CI]

14/21 (67)

22/34 (65)

20/30 (67)

28/37 (76)

Relapse rates, n/N (%) [95% CI]


5/19 (26)


7/29 (24)


3/23 (13)


1/27 (4)

Pts without follow-up data were considered not to have achieved an SVR.


Topic:  Disease Progression - General


62. Risk of Hepato-Pancreatico-Biliary Tumors Following Hepatitis C Virus Infection: a Population-based Study on U.S. Veterans

H. B. El-Serag; E. A. Engels; L. Henderson; O. Landgren; T. P. Giordano



Hepatitis C (HCV) may increase the risk of hepato-pancreatico-biliary tumors, other than hepatocellular carcinoma. Previous case-control studies in elderly Medicare recipients indicated a possible association between HCV and intra hepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extra hepatic cholangiocarcinoma (ECC) or pancreatic cancer.



We conducted a cohort study including 146,394 HCV-infected and 572,293 HCV-uninfected users of U.S. Veterans Affairs healthcare facilities. We used the inpatient, outpatient, and death files of the national computerized VA administrative databases. Patients with two visits with a diagnostic code for HCV infection from 1996-2004 were included, as were up to four HCV-uninfected subjects for each HCV-infected subject, matched on age, gender, and baseline visit date. Risks of ICC, ECC, pancreatic cancer, and hepatocellular carcinoma were assessed using proportional hazards regression, adjusting for selection factors, race, use of medical services, and potential confounders. Chart review of 62 ECC and ICC cases indicated a high positive predictive value for the algorithm used to identify cholangiocarcinoma (85.7% for ICC, and 73.5% for ECC).



There were 75 cases of ECC, 37 ICC, 617 pancreatic cancer, and 1679 hepatocellular carcinoma during follow up that started 6 months following index date. Risk for ICC was elevated with HCV infection with (Hazard ratio (HR): 2.50 (95% CI: 1.29-4.86)). The adjusted hazard ratios (aHR) ranged between 2.07 and 2.76 adjusting for cirrhosis, diabetes, IBD, hepatitis B, alcoholism or alcoholic liver disease (up to 3 covariates at a time).


We found no increased risk for ECC (HR 1.05; 0.60-1.85). The risk of pancreatic cancer was slightly elevated (HR: 1.23, 1.02-1.49), but was attenuated when adjusting for acute or chronic pancreatitis or alcoholism (aHR 1.18; 0.97-1.42). As expected, the risk of hepatocellular carcinoma associated with HCV was very high (HR 14.8; 13.2-15.6).



·        HCV infection confers more than two-fold elevated risk of ICC.

·        There does not appear to be an association between HCV and ECC,

·        The association with pancreatic cancer needs further study.


S1000. Identification of Novel Biomarker Profiles in Hepatitis C Positive Liver Cancer Patients.

J. Petersen; K. Kasturi; C. Elferink; M. Hassan; E. Fung; T. Yip; N. Snyder



Hepatocellular carcinoma (HCC)in patients with HCV related cirrhosis occurs with a annual frequency of 1-8%. Although the prognosis for patients with advanced HCC is poor, if detected early, successful treatment by transplantation, resection, or radiofrequency ablation is possible. Currently used biomarkers for HCC are frequently normal or in the indeterminate range. Thus, the identification of a biomarker or a series of biomarkers that could identify early stage HCC would be of great interest. ProteinChip technology (SELDI-TOF) has been used as a profiling technique to identify potential biomarkers which may represent proteins, protease-cleavage products, or novel peptides. We used this technology to investigate differences in the serum profile of patients with chronic HCV from patients with HCV associated HCC.


Materials and Methods:

With IRB approval we analyzed serum samples from 60 HCV positive patients, 30 with confirmed HCC and 30 with various stages of fibrosis (6 each with F0, F1, F2, F3, and F4) without evidence of liver cancer. The samples were prefractionated using Equalizer® bead protein biomarker discovery technology and SELDI ProteinChip® array profiling. The fractions were analyzed on the PCS 4000 time of flight mass spectrometer using CM10, IMAC (pretreated with Cu), and Q10 chips. Pooled normal human plasma was analyzed concurrently as controls and to establish criteria for peak magnitude significance. Data of the proteomic spectra was analyzed by Ciphergen Express Data Manager software with Pattern Track and Two-way Hierarchical Clustering algorithm.



We were able to identify 91 peaks of <50 KDa that were significantly correlated (p<0.05) with the presence of HCC. These peaks were then analyzed using logistic regression (Insightful Miner v 3.0, Insightful Corporation Seattle, WA, USA). In this manner we were able to identify 7 peaks of < 20 KDa that allowed the separation of precancerous HCV-positive patients from HCV-positive HCC patients. Additional analysis of the profile revealed that the magnitude of these peaks was greater in the HCV positive patients without evidence of HCC. The average peak height average for HCV patients ranged from 2.17 – 17 times greater than that found for the HCC patients. Using these peaks the sensitivity and specificity for detection of HCC was 100%.



We were able to identify 7 peaks of <20 KDa that allowed us to separate patients with HCC from HCV positive patients without evidence of HCC. Additional work to identify these putative biomarkers along with the development of assays will be necessary to evaluate their usefulness in the early detection of HCC.


S1004. A Comparison of Alphafetoprotein, AFP-L3% and Des-Gamma Carboxyprothrombin in Patients with Chronic Hepatitis, Cirrhosis and Hepatocellular Carcinoma. 

F. A. Durazo; M. J. Tong; L. M. Blatt; W. G. Corey; J. Lin; S. Han; S. Saab; R. W. Busuttil



Hepatocellular carcinoma (HCC) is a common complication in patients with cirrhosis of the liver. Detection of HCC at an early stage is critical for a good clinical outcome. Surveillance of patients at risk to develop HCC is crucial.



a)     compare the accuracy of alphafetoprotein (AFP), AFP-L3% and des-gamma carboxyprothrombin (DCP) in the diagnosis of HCC in patients with chronic viral hepatitis and with cirrhosis;

b)    define the level of each tumor marker with the best sensitivity, specificity, and positive predictive value (PPV) for the diagnosis of HCC.



243 patients with either chronic hepatitis B (HBV) or chronic hepatitis C (HCV) were included in the study. Forty eight had stage I-III fibrosis on liver biopsy, 49 had cirrhosis and 146 had HCC.



Levels of AFP, AFP-L3% and DCP were significantly higher in patients with HCC than in patients with chronic hepatitis or cirrhosis (p=<.0001). ROC curves indicated that the cut-off value with the best sensitivity and specificity for each test was ≥25 ng/mL for AFP, ≥10% for AFP L3% and ≥84 mAU/mL for DCP. The sensitivity, specificity and PPV of AFP was 69%, 87% and 69.8%, of AFP-L3% 56%, 90% and 56.1% and of DCP 87%, 85% and 86.8% respectively. In contrast to AFP and AFP-L3%, DCP levels were below the ROC cut-off in all patients without HCC. No advantage was observed when combining two or three of the tumor markers.



DCP was superior to AFP and AFP-L3% in differentiating patients with HCC from chronic viral hepatitis and from cirrhosis, and it should replace AFP as a tumor marker for HCC. The clinical utility of AFP-L3% is more as a confirmatory test when AFP is elevated.


AFP, AFP-L3% and DCP for the Diagnosis of Hepatocellular Carcinoma























AFP= Alpha-fetoprotein DCP= Des-gamma carboxyprothrombin (PIVKA II) PPV= Positive predictive value NPV= Negative predictive value


S1009. Prognosis of Patients with Hepatocellular Carcinoma Detected by Surveillance Program.

T. Sato; R. Tateishi; H. Yoshida; T. Ohki; H. Nakagawa; R. Masuzaki; J. Imamura; N. Yamashiki; T. Goto; H. Yoshida; F. Kanai; S. Shiina; T. Kawabe; M. Omata



In Japan, around 80% of hepatocellular carcinoma (HCC) develop due to chronic hepatitis C virus, thus periodical screenings intended for early detection of HCC have been widely employed among these high risk groups. We investigated the prognosis of patients with hepatocellular carcinoma detected by surveillance program.



We enrolled consecutive 1431 patients between 1994 and 2004, who were positive for HCV, negative for HBsAg, and without HCC at the first visit. We identified HCC among 340 patients during 5.4 yrs of mean follow up period (AASLD2006). Among these patients with HCC, we analyzed 243 patients who received all screening (ultrasound and alfa-fetoprotein (AFP)) at our institution at intervals shorter than 6 months periodically. Diagnosis of HCC essentially depended on arterial enhancement along with venous washout on computed tomography (CT) scanning. Hypovascular tumor was followed up, and pathological diagnosis was provided when the tumor had grown larger. Treatment procedure was transarterial embolization/surgical resection/percutaneous transhepatic ablation/best supportive care in 35/18/187/3. Cumulative survival time was assessed, considering factors including age, sex, albumin, bilirubin, prothrombin time (PT), AFP, platelet count, size and number of tumors. Kaplan Meier method was used for survival time analysis after the initial treatments of HCC. Univariate and multivariate Cox proportional hazard regression analyses were applied to assess the significance of each factor.



There were 152 men and 91 women with the median age of 67 yrs, Child –Pugh score was A/B/C in 149/85/9. Tumor size was 1.7±0.6cm when detected, and 2.2±0.9cm when treated. Ninety patients were died during the observation period (mean 4.9 yrs). Survival at 3 yrs, 5yrs, 8yrs, 10yrs was 74.4%, 51.94%,  42.3% and 23.2% respectively. Univariate analysis revealed that age, Child-Pugh classification, AFP, platelet count, and size and number of tumors, and AFP were statistically-significant independent risk factors for survival. 



HCC was detected early enough for efficient treatment owing to surveillance program, and patients achieved good survival rates. However, the survival curve showed an accelerating drop later simulating wearout failure model. To obtain more than 10 yrs survival, strategies in addition to the surveillance program for early detection of HCC are strongly required.


S1011. Prognostic indicators of death in patients (pts) with cirrhosis and hepatocellular carcinoma (HCC) – A systematic review of 64 studies.

P. Tandon; G. Garcia-Tsao



In the West, HCC occurs mainly in the setting of cirrhosis. Although there are many studies of predictors of death in HCC, most combine pts with and without cirrhosis.



To perform a systematic review of the literature evaluating predictors of death in pts with cirrhosis and HCC and to evaluate whether predictors differ between pts with compensated and decompensated cirrhosis.



All prognostic studies of HCC were considered eligible if they met the following criteria:

a)     publication in English;

b)    inclusion of adult pts;

c)      >80% of pts had cirrhosis;

d)    follow-up >6 months;

e)     multivariable analysis performed.

Quality was based on widely accepted quality criteria for prognostic studies. Criteria used to select “good” quality studies were: inclusion of consecutive pts, relevant baseline characteristics and number of deaths reported, no model overfitting.



Of 832 references obtained through a MEDLINE search, 726 were excluded because they were irrelevant or did not meet inclusion criteria (~20% of relevant articles were excluded because <80% of pts had cirrhosis). A total of 21,308 patients were included in 64 selected studies (median, 177/study); 77% male; median age was 64; 64% had HCV cirrhosis; 54% were Child Pugh class A and 52% had an “advanced” tumor (pre-defined criteria). The most common predictors of death are shown in the Table. Sensitivity analysis using only 13 “good” studies yielded the same variables. In studies that included mostly compensated pts, predictors related to liver disease predominated, while in studies that included mostly decompensated pts, predictors were both liver- and tumor-related. However, these studies were few and results are not robust.



·        This systematic review of 64 studies shows that the most robust predictors of death in pts with cirrhosis and HCC are liver-related (Child-Pugh class and bilirubin) and tumor-related (size, AFP, portal vein thrombosis).

·        Multiple limitations of the analyzed studies were identified:

o       No trial met all quality and only 13 trial (20%) met the 4 major quality criteria.

o       Inclusion of both cirrhotic and non-cirrhotic patients.

o       Heterogeneous inclusion of patients varying level of patients at varying levels of hepatic decompensation.

·        Future prognostic studies of HCC:

o       Should be performed in specific patients populations with a different overall prognosis.

§        With or without cirrhosis

§        Compensated or decompensated cirrhosis.

o       Should include 6 predictors of death identified in this review.



N of studies in which variable was among the first 5 significant variables

N of studies evaluating the variable

% of studies in which variable was among first 5 / studies that evaluated variable

Portal vein thrombosis




Tumor size




Alfa fetoprotein (AFP)




Child Pugh class








CLIP score





CLIP (Cancer of the Liver Italian Program); consists of portal vein thrombosis, tumor size, AFP and Child Pugh score


S1016. Changes Of Cytokines In Liver Cirrhosis Patients With Advanced Hepatocellular Carcinoma Treated By Combined Intra-Arterial Chemotherapy.

H. Nagai; D. Miyaki; T. Matsui; M. Kanayama; K. Higami; K. Momiyama; T. Ikehara; K. Matsumaru; M. Watanabe; K. Ishii; Y. Sumino; K. Miki



We have reported that combined intra-arterial chemotherapy prolongs the survival of liver cirrhosis (LC) patients with advanced HCC (aHCC) (DDW 2007, LA). Tumor necrosis factor (TNF) is known to induce cancer cell-specific apoptosis by binding to a TNF-related apoptosis-inducing ligand. Binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes is also known to induce apoptosis.



The aim of this study was to clarify changes of cytokines in LC patients with aHCC receiving combined intra-arterial chemotherapy.



Nineteen adult Japanese LC patients with aHCC were treated with combined intra-arterial chemotherapy between 2005 and 2006 at our hospital. Their tumors were inoperable, as assessed from computed tomography findings. Continuous infusion chemotherapy (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was performed via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. Blood samples were collected from the patients in the early morning both before and after chemotherapy. The serum levels of TNF-alfa, soluble TNF-receptor (TNF-R), Fas ligand, soluble Fas, and NK cell activity were evaluated.



Thirteen of the 19 patients (group R) showed a partial response (5 patients) or stable disease (8 patients), although 6 of the 19 patients (group N) showed no response. The mean age was 69.5 years in group R and 62.5 years in group N. There were 10 patients with HCV-related LC and 3 patients with alcoholic LC in group R. There were 2 patients with HCV-related LC and 4 patients with HBV-related LC in group N. The serum level of TNF-alfa was lower after chemotherapy than before chemotherapy in group N (p<0.05, Wilcoxon’s test). There was no difference in the serum levels of TNF-R between before and after chemothrapy. Moreover, there was also no difference between the 2 groups (Mann-Whitney test). The serum level of Fas was higher after chemotherapy than before chemotherapy in group N, while there was no difference of serum Fas ligand levels between before and after chemotherapy. Furthermore, there was no difference of NK cell activity between before and after chemotherapy.



These results indicate that maintenance of a high serum level of TNF-alfa and Fas expression on HCC in LC patients with aHCC might be important to achieve success with combined arterial chemotherapy.


S1017. Role of combined Chemoembolisation/ Radiofrequency Ablation in the treatment of large/ multifocal Hepatocellular.

N. Rajoriya; E. Leen; M. Neilson; J. Crichton; E. Forrest; J. Morris; A. Stanley



Hepatocellular Carcinoma (HCC) is the 4th commonest cause of cancer in the world. Although surgery or radiofrequency ablation (RFA) can be effective for small tumours, once the size is > 3cm effective therapies are often limited. Chemoembolisation is often used as palliative therapy for larger or multiple tumours, but there are limited data on combined chemoembolisation and RFA as therapy for this patient group.



The aim of our audit was to assess the impact/outcome of combined chemoembolisation and RFA in our centre in the management of patients with HCC > 3cm or multiple tumours.



A retrospective case note analysis was performed of patients diagnosed with HCC over a 5 year time period (January 2000-2005). Patients treated with chemoembolisation followed by RFA (combined therapy) were identified and outcome assessed.



52 were diagnosed with HCC over the study period. Aetiology was alcoholic liver disease (ALD) in 45% and 73% patients had Childs C disease. 33% had a single HCC (mean diameter 5.89 +/-2.57 cm). The overall one-year survival was 35%. 12 were treated with chemoembolisation followed by RFA (11 male; mean age 59.2+/-10.6). Aetiology included: ALD in 6 patients, Haemochromatosis in 2, Cryptogenic cirrhosis in 2, HCV in 1 and PBC in 1. The Child Pugh Grades were: 8 grade A and 4 grade B with 42% having a raised AFP at diagnosis. 50% patients had a single HCC (median diameter 6cm, range 3.5cm-20cm). None had extra-hepatic metastasis on CT +/- MR imaging. 50 % were Barcelona Clinic Liver Cancer (BCLC) Stage A, 17% stage B and 33% stage C. The median no of chemoembolisation sessions was 2 (range 1-5), followed by a median no of 2 (range 1-6) RFA sessions. The only complication encountered was a pyrexia with abnormal LFTs post-procedure in one patient which settled after antibiotic therapy. The median follow up was 29 (range 9-78) months.Following combination therapy, 75% of patients had complete radiological resolution of their HCC based on imaging at a median of 6 (range 2-25) months. 25% had a recurrence of ablated HCC and 42% had new HCCs diagnosed on follow up imaging.Overall one and two-year survival for those treated with combination therapy was 58%, and 50% respectively. The median survival for patients graded BCLC stage A, B and C was 33, 20 and 10 months.



Chemoembolisation followed by RFA therapy results in good radiological tumour resolution in patients with > 3cm or multiple HCC without metastatic disease. However recurrence and new HCC occurs frequently on follow-up. This combination therapy requires further study to clarify its exact role in the management of HCC.


S1021. Changing Characteristics of Hepatitis C Related Hepatocellular Carcinoma in Japan.  

R. Tateishi; S. Shiina; H. Yoshida; R. Masuzaki; T. Sato; T. Ohki; N. Yamashiki; T. Goto; H. Yoshida; F. Kanai; T. Kawabe; M. Omata



Approximately 80% of hepatocellular carcinoma (HCC) in Japan were due to chronic hepatitis C. Patients with hepatitis C can be considered as a fixed cohort in Japan where intravenous drug abuse is uncommon and acute hepatitis C is quite sporadic since 1990’s.



To assess the trend in the hepatocellular carcinoma (HCC) in Japan.



We analyzed characteristics of 493 patients with naïve HCC who were diagnosed between 1991 and 2005 at our institution. Patients were included if they were HCV-Ab positive and HBsAg negative and had a history of blood transfusion before diagnosis of liver diseases. Trends in age at diagnosis of HCC, male to female ratio, interval of diagnosis of HCC and blood transfusion, platelet count and liver function according to Child-Pugh classification were assessed by linear regression.



The patients consisted of 280 males and 213 females. Mean age increased from 59.6 years in 1991 to 71.6 years in 2005 (P < 0.001). Majority of patients had a history of blood transfusion in 1960's before paid blood donation was discontinued in Japan. Mean duration of infection before diagnosis of HCC also increased from 31.5 years in 1991 to 41.4 years in 2005 (P < 0.001). The proportion of higher platelet count and better Child-Pugh score also increased significantly. There was no significant trend in male to female ratio. The trends in age, duration of infection, higher platelet count and better liver function remained significant after multivariate regression analysis.



HCC with blood transfusion related hepatitis C emerges from a fixed cohort, majority of whom had a history of blood transfusion in 1960’s. The patients were getting older rapidly reflecting the aging of background population. Duration of infection tends to be longer with increasing number of patients with less advanced disease or non-cirrhotic liver.


Topic:  Disease Progression  - General


S1055  Comorbid Medical and Psychiatric Illness and Substance Abuse in HCV-Infected and Uninfected Veterans

U. A. Khan; K. McGinnis; M. Skanderson; A. Butt



We undertook this study to determine the prevalence of comorbidities (secondary diagnoses for specific complications) in HCV infected and uninfected persons.



Demographic/comorbidity data for HCV infected persons and age, race and gender matched HCV uninfected controls were retrieved from the VA National Patient Care Database using ICD-9 codes. We used logistic regression to determine the odds of comorbidities in HCV infected subjects.



We identified 126,926 HCV infected subjects and 126,926 controls. HCV infected subjects had a higher prevalence of diabetes, anemia, hypertension, COPD/asthma, cirrhosis, HBV, cancer, psychiatric comorbidities and substance abuse but a lower prevalence of coronary artery disease (CAD) and stroke.


In HCV infected persons, the odds of being diagnosed with congestive heart failure, diabetes, anemia, hypertension, COPD/asthma, cirrhosis, HBV and cancer were higher, but lower for CAD and stroke. After adjusting for substance abuse, the odds of psychiatric comorbidities were not higher in HCV infected persons. (see table)



·        The prevalence of comorbidities differs in HCV infected and uninfected veterans.

·        The association between HCV and psychiatric diagnoses is partially attributable to substance abuse.

·        These factors should be considered when evaluating patients for treatment and designing new intervention strategies.

Odds of co-morbid diagnoses in HCV-infected veterans compared with HCV uninfected veterans.


Unadjusted OR (95% CI)*

Adjusted OR (95% CI)â€

Medical Comorbidities



Coronary artery disease

0.75 (0.73-0.77)

0.74 (0.71-0.760


0.90 (0.86-0.95)

0.86 (0.82-0.90)

Peripheral Vascular Disease

0.97 (0.92-1.02)

0.95 (0.90-1.00)


1.09 (1.05-1.13)

1.15 (1.10-1.20)


1.10 (1.08-1.13)

1.20 (1.17-1.23)


1.26 (1.23-1.30)

1.05 (1.02-1.08)


1.83 (1.76-1.90)

1.53 (1.47-1.60)


12.0 (11.04-13.12)

8.24 (7.54-9.00)

Hepatitis B

21.58 (17.31-26.89)

13.34 (10.67-16.67)

Psychiatric Comorbidities




1.24 (1.20-1.28)

0.80 (0.77-0.82)


1.58 (1.54-1.62)

1.05 (1.02-1.08)

Major Depression

1.62 (1.57-1.66)

0.93 (0.90-0.96)

Mild Depression

1.73 (1.69-1.77)

1.03 (1.01-1.06)

Bipolar Disorder

1.85 (1.79-1.92)

0.96 (0.92-1.00)

Alcohol and Drug Use



Drug Use Disorder

4.71 (4.60-4.82)


Alcohol Use Disorder

3.92 (3.84-4.00)



*The two groups were matched for age (5 year blocks), race and gender. – Adjusted for age, race, gender, drug use and alcohol use.


Topic:  Diagnostic Tools – Biochemical/Imaging


S1226 Diagnostic value of biochemical markers for prediction of liver fibrosis and inflammation in pediatric patients

Y. Bujanover; R. Klar; M. Kori; E. Granot; R. Shoul; V. Nachmias



In the past several noninvasive laboratory methods were suggested as an alternative to liver biopsy.  Recently a panel of six serum markers -Fibro test(FT) – Actitest (AT) was validated in the prediction of liver fibrosis and inflammatory activity in adult patients with liver disease.



The aim of the present study was to assess the diagnostic utility of the Fibrotest – Actitest in pediatric patients with viral and autoimmune hepatitis.


Subjects and methods:

Twenty four patients were studied, 14 female, 10 male, age range 2-18 yr (m-12.4yr).


Diagnosis : HCV-13; HBV-3;HCV+HBV-1; HCV+HIV-1;Autoimmune hepatitis-4. Liver biopsy was performed in 23 patients.


Six biochemical markers were evaluated using commercial kits: Total bilirubin, GGT, alfa2 macroglobulin, haptoglobin, apolipoprotein A1, ALT. Those parameters were used for the calculation of the FT-AT scores according to the patent algorithm of Biopredictive (France) ranging from 0-1. Liver biopsy was compared to the results of the FT and AT using AUROC statistical analysis.



·        FT- 75% of the patients were F0;

·        F0-F1 12%,

·        F1- 4%,

·        F1-F2- 8%,


AT-A0 41%, A0- A1 -20%, A1- 12%, A1-A2 -20%, A3 – 4%.


The AUROC comparing FT with the liver biopsy results were:

·        0.85 for F0,

·        0.87 for F0-F1,

·        0.88 for F1-F2.


FT yielded a higher AUROC than AT .85 VS .70 respectively.



·        Fibrotest – Actitest is a simple and effective method to assess fibrosis and inflammation in pediatric patients with liver disease.

·        The correlation with liver histology was high.

·        The biochemical markers may serve as an alternative to liver biopsy in pediatric patients



Topic:  Epidemiology


S 1227  Prevalence and risk factors associated with hepatitis B and hepatitis C virus infections among healthy population in an urban community in Dhaka, Bangladesh

H. Ashraf; C. Rothermundt; N. H. Alam; P. K. Bardhan; A. Brooks; S. Hassan; N. Gyr



Prevalence data of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among healthy population in Bangladesh is rare. However, chronic HBV and HCV infected individuals remain asymptomatic for many years. A population-based study was conducted to estimate the prevalence of HBV and HCV infections including their risk factors, which might eventually guide the development of prevention strategies.



Asymptomatic subjects of either gender of all ages residing at an urban community of Kamalapur, Dhaka were randomly enrolled into the study after written consent. Information was collected on demographic, occupational and behavioural characteristics including their education, marital status, previous surgical and dental procedures and receiving injections and blood transfusions. HBV infection was diagnosed by performing HBsAg and Anti-HBc by ELISA and HCV was diagnosed by Anti-HCV screening test (ELISA-3).



From June 2005-April 2006, 1844 healthy subjects were enrolled, 37% males, 22% gave previous history of jaundice.


·        HBsAg was positive in 121 (6.6%) subjects: 14 (0.8%) were only HBsAg positive and 107 (5.8%) were both HBsAg and Anti-HBc positive. Only Anti-HBc was positive in 420 (23%) subjects and,

·        HCV was positive in 9 (0.5%) subjects: 4 (0.2%) were only Anti-HCV positive and 5 (0.3%) were both Anti-HCV and Anti-HBc positive.

·        About half of the HBV positive subjects were between ages 20-40 years, which was rare (4%) among under-5 children.

Some factors such as were significantly associated with HBV infection:

·         previous jaundice (OR 1.33; p=0.01),

·        exposure to a community barber for shaving (OR 2.29; p=0.00),

·        received treatment from unregistered health care providers (OR 1.44; p=0.005),

·        received treatment for sexually transmitted diseases (OR 1.77; p=0.002),

·        being married (OR 2.23; p=0.00), and

·        multiple sex partners (OR 2.57; p=0.00)


Some additional factors such as were significantly associated with HBV infection:

·        receiving illicit drug injections (OR 11.86; p=0.01),

·        needle-stick injuries (OR 2.11; p=0.001),

·        needle piercing of ear, nose and body (OR 1.3; p=0.01),

·        surgical operation (OR 1.3; p=0.02),

·        circumcision (OR 1.47; p=0.00) and

·        animal bites (OR 1.68; p=0.00) like dog, cat, monkey-bites



·        The finding of the study demonstrates a high endemicity of HBV infection in an urban community in Dhaka, Bangladesh.

·        However, HCV infection is rare.

·        Prevention of HBV infection in Bangladesh is urgently necessary by hepatitis B vaccination and creating public awareness for practicing one-time-use-only needles and syringes and ensuring safe blood transfusions and maintaining strict aseptic precautions during surgical and dental procedures.

Topic:  Treatment – General


S1231  Peginterferon Alfa 2a / Ribavirin Versus Peginterferon Alfa 2b / Ribavirin Combination Therapy In Chronic Hepatitis C Genotype 3

A. Q. Khan; A. Awan ; S. Shahbuddin ; Q. Iqbal


Editor’s note:  This is an interesting study, but the patient population is too small to draw any conclusions about the efficacy of either product.



Hepatitis C virus (HCV) genotype 3 account for up to 80% of HCV infection in Pakistan. The purpose of the present study was to compare the efficacy and safety of Peginterferon Alfa 2a / Ribavirin combination therapy with Peginterferon Alfa 2b / Ribavirin combination therapy in Chronic Hepatitis C genotype 3 patients.


Material and Methods:

In an open randomized controlled trial 66 naïve Chronic Hepatitis C genotype 3 patients were randomized to receive Peginterferon Alfa 2a 180 ug/weekly plus Ribavirin 800 mg/day (33 pt group I) or Peginterferon Alfa 2b 1ug/kg/body wt/weekly plus Ribavirin 800 mg/day (33 pt group II) for 24 weeks. Both groups were comparable for age, sex, baseline ALT level, albumin level, viral load, and genotype 3 subtypes. Primary end point was loss of HCV RNA at 24 weeks after stopping the treatment (SVR).



Of these 66 patients: 60 patients (30 in each group) completed the trial (2 patients (1 in each group) were lost to follow up, 1 patient in group I developed hyperthyroidism, 2 patients (1 in each group) developed severe thrombocytopenia and one patient in group II developed severe neutropenia). 


Reduction of peginterferon dosage were required in 4 patient (2 in each group) and reduction of ribavirin dosage were required in 3 patients (2 in group I and 1 in group II).


End of treatment response (ETR) in group I and II was 26 (86.6%) and 27 (90%) patients respectively. Sustained virologic response (SVR) in group I and II was 26 (86.6%) and 27(90%) patients respectively.



Both Peginterferon Alfa 2a / Ribavirin and Peginterferon Alfa 2b / Ribavirin regimens were similar in efficacy and safety in Chronic HCV genotype 3 patients.


Topic:  Treatment – General


S1232  Efficacy of a 72-week course of treatment for previous relapsers to PEG/ribavirin therapy

J. McMahon; S. C. Gordon


Editor’s note:  This study is interesting because it attempts to individualize treatment, but there is too small of a patient population to draw conclusions.



Patients who relapse after 48 weeks of PEG/ribavirin treatment represent a difficult therapeutic challenge. No guidelines exist concerning the proper management of these individuals. Two recent studies showed lower relapse rates following 72 vs. 48 weeks of therapy among treatment naïve candidates. It is unknown, however, whether a longer duration of re-treatment will achieve SVR among previous relapsers. We assessed our preliminary experience using a repeat course of extended PEG/ribavirin in patients who previously relapsed after 48 weeks of PEG/ribavirin.



Four consecutively evaluated HCV patients (3 genotype 1, 1 genotype 2), who relapsed following an initial 48-week course of PEG/ribavirin, underwent re-treatment for 72 weeks. During their initial therapy, 3 of 4 patients became negative within the first 16 weeks, and all four patients maintained >80/80/80 adherence. None of the patients required growth factors at any time. Following initial therapy, all 4 relapsed within 12 weeks of their last dose. Each was then re-treated with PEG-IFN alfa 2a 180 mcg once weekly plus ribavirin (>13.3 mg/kg/day) for 72 weeks. We assessed HCV RNA using Amplicor 2.0 quantitative and reflex TMA qualitative testing.



During re-treatment, each patient became HCV RNA negative by treatment week 12, and maintained viral negativity for the duration of treatment. Six months after completing re-treatment, each patient remained HCV RNA negative, thus now achieving a recognized SVR. Extended duration therapy was well tolerated; 2 of the 4 patients received higher doses of ribavirin based on weight, and no patient required dose reductions due to adverse events.



1.     SVR is attainable among patients who relapse following 48 weeks of PEG/ribavirin therapy.

2.     72 weeks of re-treatment was well tolerated in this group of motivated patients.

3.     Two of these patients received higher doses of ribavirin during re-treatment, thus ribavirin dosing may affect the ability to achieve SVR.

4.      Each patient remained adherent during both regimens, thus the duration of viral negativity appears to represent a pivotal goal.

5.      Patients who relapse after 48 weeks of PEG/ribavirin should be considered for re-treatment with a longer duration regimen.







Previous Treatment

Re-Treatment Baseline Viral Load






Peg2b/riba 800mg







Peg2b/riba 800mg







Peg2a/riba 1200mg







Peg2b/riba 1200mg



S1233.  Factors associated with adherence to combination therapy of interferon and ribavirin for patients with chronic hepatitis C: Importance of patient selection and treatment experience

D. Tanioka, Y. Iwasaki, K. Takaguchi, H. Ikeda, R. Okamoto, Y. Araki, M. Ando, T. Shimoe, N. Hashimoto, K. Kita, M. Tomita, Y. Makino, H. Kobashi, K. Sakaguchi, Y. Shiratori1


Background/Aims: A combination therapy of interferon (IFN) or pegylated IFN plus ribavirin achieves higher rate of sustained virologic response than IFN monotherapy. However, poor adherence is one of the most important problems, especially in older patients. In this study, we analyzed factors that might have effect on adherence to therapy in patients who had initial or re-treatment of IFN therapy.



We consecutively enrolled 363 patients (221 were IFN naïve and 142 were undergoing re-treatment) with chronic hepatitis C. Mean age of naïve and re-treatment groups were 54.8 and 55.7 years, respectively. IFN alpha-2b was administered daily for two weeks, followed by three times per week for 22 weeks, while ribavirin was administered daily. We evaluated tolerability in terms of treatment adherence to the 80/80/80 rule. Logistic regression analysis was performed to analyze the factors associated with adherence to combination therapy.



Of 363 patients, 189 (52%) achieved 80% adherence. Multivariate logistic regression analysis revealed that re-treatment, center with more patients (>=30 cases) enrolled, patients age (<55 years), body weight (<60 kg), genotype 2, hemoglobin concentration (>=14 g/dL), and dosage of IFN per weight (<0.13 MIU/kg) were associated with achievement of 80% adherence to combination therapy. Accordingly, the achievement of 80% adherence was more frequent in re-treatment (61%) than in naïve group (46%) (p<0.01), in centers with more patients enrolled (57%) than in less patients enrolled (46%) (p=0.03).



·        Retreatment group and patients treated in center with more patiens tested had different background from others.

·        In these groups, dose reduction and discontinuation rate of interferon and ribavirin were lower and adherence was higher.

·        There was no significant difference in SVR rate in spite of different background.

Topic:  Treatment—Disease Progression


S1240 Sustained virologic response to previous interferon treatment may reduce the risk for the recurrence of hepatocellular carcinoma in patients with hepatitis C

H. Miyatake; Y. Kobayashi; Y. Iwasaki; S. Nakamura; R. Terada; K. Miyoshi; H. Ohnishi; S. Iwadou; B. Shoji; K. Kuwaki; J. Toshimori; T. Yasunaka; H. Hagihara; K. Sakaguchi


Background and Aims:  

It has been reported that interferon (IFN) treatment for chronic hepatitis C could prevent the development of hepatocellular carcinoma (HCC).  HCC are liable to recur frequently even after curative therapy mainly because of multi-centric occurrence. The purpose of this study was to clarify the effect of previous IFN treatment before the development of HCC on the recurrence and survival of HCC patients.



Three hundred and eighty-two out of 897 patients with HCC diagnosed at Okayama University Hospital between 1995 and 2005 underwent curative treatment for HCV-related HCC. One hundred and eighteen who had received IFN treatment before the development of HCC were compared with the other 264 patients (IFN untreated group). Seventeen of IFN treated group were sustained virologic responders (SVR), and the other 101 patients were non-SVR. Twelve out of 101 patients were sustained biochemical responders (SBR). Survival rate and the 1st and 2nd recurrence rate after curative treatment for HCC were statistically analyzed. Risk factors for HCC recurrence were analyzed by Cox proportional hazards model.



Mean follow-up period of all patients was 6.2 years. IFN treated group comprised 70 men and 48 women, and mean age at IFN therapy and development of HCC was 58 and 65 years old, respectively.


One hundred out of 118 patients (85 %) were classified into Child-Pugh classification A. IFN untreated group comprised 182 men and 82 women, and mean age at development of HCC was 67 years old. Survival rate of SVR was higher than that of non-SVR and IFN untreated patients (p=.010).


The 1st HCC recurrence rate was similar between SVR and non-SVR. However, the 2nd HCC recurrence rate in SVR at 2 years was significantly lower than that in non-SVR (0% vs. 68%, p=.006). There were no significant difference in the survival rate and the 1st and 2nd recurrence rate between SVR and non-SVR.


In multivariate analysis, the age at the time of IFN therapy (p=.043) and tumor number at HCC development (p=.044) were independent factors related to 1st HCC recurrence, while sustained virologic response (p=.057) were related to 2nd HCC recurrence.



Sustained virologic response to previous interferon treatment in patients with hepatitis C may reduce the risk for the second recurrence of HCC and improve survival.


Topic:  Treatment—Disease Progression


S1728  The Prevalence and Significance of Occult Hepatitis B In A Liver Transplant population with Chronic Hepatitis C

K. Shetty; M. T. Hussain; L. Nei4; K. Reddy; A. Lok



Occult hepatitis B virus(HBV)is defined as the detection of HBV DNA in the serum or liver of those who test negative for hepatitis B surface antigen (HBsAg).It has been implicated in HBV reactivation within immunosuppressed populations, and in the development of hepatitis C virus (HCV)-associated cirrhosis and hepatocellular carcinoma (HCC) in non-transplant settings. The significance of occult HBV following orthotopic liver transplantation (OLT) is incompletely understood.



1.     Determine the prevalence of occult HBV in a HCV-infected transplant population

2.     Examine the course of occult HBV post- orthotopic liver transplantation

3.     Assess the effect of occult HBV on the histological recurrence rate of post- orthotopic liver transplantation HCV



Those with HCV cirrhosis listed for orthotopic liver transplantation were prospectively followed.  PCR techniques were utilized to test for serum HBV DNA at enrollment, within the explant and at 8 and 24 weeks post- orthotopic liver transplantation.



56 patients with HCV cirrhosis were enrolled, 44 underwent OLT.  The overall prevalence of occult HBV based on positive serum HBV DNA was 8/56(14%) and based on positive hepatic HBV DNA was 19/44(43%). The presence of serum hepatitis B core antibody (anti-HBc) and a history of injection drug use correlated with occult HBV. Explant-proven HCC was found in 63% of patients with occult HBV compared to 32% of those without occult HBV (p = 0.02, odds ratio 4.3)(table 1). An overall histological HCV recurrence rate of 51% was noted, with no significant difference between groups.  Multivariate analysis showed HCV recurrence to be associated with donor age, and HCV viral load. No detectable serum or explant HBsAg was noted at 8 or 24 weeks in any patient.



Occult HBV is far more prevalent in patients with end-stage HCV than would be expected from its prevalence in the general population. It is strongly associated with the presence of anti-HBc, history of injection drug use and explant-proven HCC. No effect of occult HBV is noted on HBV reactivation, HCV recurrence or post- orthotopic liver transplantation patient survival.

Comparison of demographics/HCV recurrence


Occult HBV


No Occult HBV


p Value

Mean age
at OLT


















Anti-HBc positive(%)






Anti HBs positive(%)












HCC (%)






Recurrent HCV(%)






IVDA : intravenous drug abuse;ACR : acute cellular rejection.* p = significant 


Topic:  Liver Transplantation –Liver Transplantation - General


S1729. Effect of Pre-Transplant Hepatitis C Virus RNA Status on Post-Transplant Outcome.

C. G. Nudo; R. Cortez; D. Wepler; A. G. Tzakis; A. Regev View Pres.



Low or undetectable hepatitis C virus (HCV) RNA before liver transplant (OLT) have been shown to lead to decreased rate of HCV recurrence after orthotopic liver transplantation.



To determine whether patients with undetectable HCV RNA (RNA-) or detectable HCV RNA (RNA+) at the time of orthotopic liver transplantation differ in HCV recurrence, graft or overall survival.



A retrospective chart review of patients transplanted for HCV cirrhosis was performed. Data collected included:  MELD score, recipient/donor age, recipient/donor sex, pre-transplant HCV RNA, post-transplant HCV recurrence (viral/histological), patient and graft survival.



Between July 1995 to July 2004, 49 patients were HCV RNA- at orthotopic liver transplantation.   48 HCV RNA+ patients at the time of orthotopic liver transplantation were analyzed as a control group.  All HCV RNA- patients were negative as a result of combination therapy with interferon/pegylated interferon and ribavirin, which was discontinued before orthotopic liver transplantation. There was no difference in recipient gender (male 63% vs 62.5%), recipient age (51.6+/-9.9 vs 53+/-8.45), donor gender-male (67% vs 50%), or donor age (40.7+/-13.7 vs 41.9+/-18.6) between the HCV RNA- and HCV RNA+ groups respectively. The mean duration of follow-up after orthotopic liver transplantation was 50.6+/-36.9 vs 40.8+/-18.7 months for the HCV RNA- and HCV RNA+ groups. 69% of patients in the HCV RNA- group developed virological recurrence during follow-up. There was no difference in the incidence of histological recurrent hepatitis C between the HCV RNA- and HCV RNA+ groups (55.6% vs 56%). However, the HCV RNA+ group had a lower time to histological recurrence (8.45+/-8.6 vs 18+/-19 months, p=0.02). There was no difference in rate of death (20.8% vs 28.6%), but there was a trend toward a higher rate of graft failure in the HCV RNA+ group (12.5% vs 2%, p=0.059). In the HCV RNA- group 31 of the 49 subjects received a graft from a same gender donor.


The patients who received an opposite gender graft had a higher rate of histological recurrence of hepatitis C (72.2% vs 38.7%, p=0.038). In the HCV RNA+ group there was no difference in rate of histological recurrence between gender mismatched and matched groups (59% vs 53.8%, p=0.78). In the combined group of HCV RNA+ and HCV RNA-, there was a trend towards a higher rate of histological recurrence in the gender mismatched group when compared to the matched group (65% vs 45.6%, p=0.067).



·        Patients transplanted for HCV cirrhosis with undetectable HCV RNA (HCV RNA -) had lower rate of virologic recurrence (55% vs. 100%, p=0.0001), a trend toward a lower rate of histological recurrence (36.7% vs. 56.3%, p=0.068), and longer time to development of histological recurrence (medium 11 vs. 5.6 months, p=0.03), when compared to patients with detectable HCV RNA (HCV RNA +).  These results were unrelated to SVR.

·        Patients with SVR had a statistically lower rate of virolgoical recurrence and histological recurrence when compared to patients with no SVR/RNA (-) or RNA (+).  All patients with SVR had no virological recurrence or histological recurrence post transplantation.

·        All HCV RNA negative subjects who received a liver graft from donors of the same gender had a trend toward a higher histological ree survival (logrank p=0.051)

·        Furthers studies are needed to evaluate these findings.

Liver Transplantation – General


S1731. Extended Donor Criteria Liver Allografts Maximize Donor Utility and Access to Transplantation. 

I. J. Lo; C. Kin; B. Alkofer; J. V. Guarrera; B. Samstein; L. Ratner; D. Jan; S. Bellemare; M. Kinkhabwala; J. C. Emond; J. F. Renz.



Liver transplantation (LTX) is limited by a donor shortage. Utilization of allografts that do not meet traditional criteria (extended donor criteria [EDC]) offers immediate expansion of the donor pool. EDC allografts are allocated by transplant center rather than wait-list priority (UNOS).



To maximize access to LTX, 200 EDC allografts were systematically applied to an adult wait-list population from 04/01 through 01/06 while 130 patients received a UNOS allograft (mean follow-up:3.2yr).  EDC allografts included: age>65years, donation after cardiac death, hepatitis C positive (HCV), hepatitis B core antibody positive, human T-cell lymphotrophic virus positive, split-liver allograft, serum [Na]>155meq/dl, history of carcinoma, macrovesicular steatosis>40%, and behavioral high-risk donors. EDC recipients demonstrated a higher incidence of HCV liver disease, hepatocellular carcinoma (HCC), and significantly lower (p<0.01) model for end stage liver disease (MELD) score at LTX (Table #1).



Over half of EDC recipients admitted from home for LTX had been hospitalized within the preceeding 90days for complications of liver failure. Wait-time between groups was significantly lower for EDC (p<0.01).


No significant difference in the incidence of complications categorized as biliary, vascular, wound, and delayed or primary graft nonfunction was observed. Log-Rank analysis of Kaplan-Meier survival estimates demonstrated no significant difference in patient or graft survival at 6months; however, EDC death secondary to recurrent HCV, HCC or co-morbidities contributed to lower one-year survival. Length of stay was significantly lower for EDC recipients. Of 543 listings during the study period, EDC increased patient access by 77%. Allocation of EDC by our transplant center reduced patient wait-list removals secondary to death by over 50% compared to regional data for each year of the study (p<0.01).



In conclusion, EDC liver allografts maximize utility of the existing donor pool and increase access to LTX while providing satisfactory results to select recipients.






MELD +/- S.D.

22 +/- 11

25 +/- 12*

LOS +/- S.D. (d)

12 +/- 9

27 +/- 31







1 MONTH (%)



6 MONTH (%)



12 MONTH (%)






1 MONTH (%)



6 MONTH (%)



12 MONTH (%)





Topic:  Liver Transplantation –Race/ Ethnicity 


S1732. Blacks have worse graft and overall survival at 2 years after OLT in the MELD era.

A. N. Ananthakrishnan; K. Saeian.


Background / Aims:

Beginning February 28 2002, the Model for End-stage Liver disease (MELD) score was introduced to better allocate donor livers. Racial differences in orthotopic liver transplantation (OLT) outcomes prior to this time have been attributed to later listing of some racial groups and more severe disease in blacks at the time of listing for orthotopic liver transplantation. The aim of our study was to evaluate if there are racial disparities in outcomes after orthotopic liver transplantation in the MELD era.



We analyzed the United Network for Organ Sharing (UNOS) database for adult liver transplants performed between February 28, 2002 and March 07, 2006. A total of 18,684 individuals were included in our study. We included demographic information, specific co-morbidities, and underlying liver disease and related complications. Race was classified into four categories – white, black, Hispanic, and other races. Our primary outcome was patient and graft survival at 24 months. Multivariate Cox proportional hazards regression was performed to identify independent predictors of survival.



There were 13,891whites, 1,557 blacks, 2,198 Hispanics, and 1,038 transplant recipients belonging to the other races. Patients in the age group 50-64 years formed just over half the study population with more males than females in each racial subgroup.


Patients with HCV formed the largest proportion of subjects undergoing liver transplantation in each racial subgroup (range 22.3-40.8%). Compared to whites, blacks had a higher proportion of patients undergoing transplantation for acute liver failure (12.3% vs. 6.7%, p<0.05) and HCV (37.6% vs. 34.3%, p <0.05).


On multivariate analysis, blacks had lower overall (HR 1.22, 95% CI 1.02-1.44) and graft survival (HR 1.27, 95% CI 1.11-1.46) compared to whites. This disparity in outcomes persisted after inclusion of either the MELD score at listing or at transplant in our final model. There was no significant difference in overall or graft survival between blacks and whites at 3 months and 12 months. Compared to whites, blacks transplanted for hepatitis C (0.72 vs. 0.80, p=0.02) or hepatocellular carcinoma (0.60 vs. 0.76, p=0.02) had significantly lower survival rates at 2 years.



·        In the MELD era, black patients have survival rates similar to whites in the first year after orthotopic liver transplantation, but have significantly lower survival at two years, especially for hepatitis C and hepatocellular carcinoma.

·        This disparity is unlikely to be attributable to severity of liver disease at the time of listing or transplant as persists after adjustment for the MELD score and medical condition at the time of transplant.

·        Thus other factors contributing to these differences, whether biologic or socioeconomic, require further investigation.

Topic:  Liver Transplantation – General


S1735. Distinct Differences in Global Immune Cell Function Profiles Between HCV(+) and HCV(-) Post-liver Transplant Patients.. 

H. Kwok; N. Chang; J. Weissman; E. S. Franco; Z. Kayali; P. W. Baron; O. Ojogho; M. H. Mendler.



We hypothesized that global cellular immune function (ImmuKnow®(I), Cylex® Immune Cell Function Assay measuring serum CD4+ ATP activity) differs according to cause of pre-liver transplantation disease and changes over time after liver transplantation.  



We reviewed a single center liver transplant cohort where I was performed from 2/05 to 7/06. Data included: demographics and liver disease; and for each I level (event), time from Liver transplant (TFT), immunosuppressants and diagnosis.



114/196 (58.2%) patients were included; 69% males; 37% Caucasians, 4% Asians, and 54% Hispanics; liver transplant at age 51yo (4-71); for HCV(58%), alcoholic liver disease (41%), HCC/liver cancer (16%), and others(33%). 477 events were obtained; 3 (1-17) per patient, 25m (4d-19y) TFT.


Diagnoses were:

·        normal allograft function (n=166, 35%),

·        recurrent disease (n=199, 42%),

·        septic event (n=34, 7%),

·        undetermined (n=27, 6%) and

·        other (n=51, 11%). 


HCV led to 188/199 (94%) of cases of recurrent disease; 188/281 (67%) of HCV patients developed recurrent disease.  The I distribution was non-Caucasian with a median of 162 (1-761). As shown below, the range of I levels in HCV (+) patients were constant over TFT, but levels in HCV (-) patients were initially high and later decreased to similar levels as HCV(+) patients.


Those with recurrent HCV on treatment had lower levels [n=10; 63.5(3-146)] as compared to those off-treatment [n=178; 147(1-563), p=0.0036] or without recurrence [n=58; 155(7-563), p=0.0034]. Also, similar TFT-dependent profiles were observed for the ratio of I/Lymphocytes (L) 103/µL [I/L ρgATP/103cells, 113.5(0.53-2012), and I/L was significantly lower in patients with recurrent HCV.



Global cellular immune function (ImmuKnow®) post-liver transplant appears depressed at baseline in HCV(+) patients as compared to other liver diseases, and even more so in HCV(+) with recurrent disease and on treatment. These differences narrow with increased time from transplantation.


Topic:  Liver Transplantation—Allocation - General


S1736. Impact of Extended Criteria Donor Livers on Survival of Patients with Hepatocellular Carcinoma.

A. Cooper; R. S. Mangus; M. Maluccio; R. Vianna; J. A. Fridell; A. Tector.



Liver transplantation is the most effective treatment for patients with hepatocellular carcinoma (HCC), with optimal outcomes in those meeting Milan criteria. With a growing shortage of donor livers, patients outside Milan criteria are rarely transplanted, though these patients have improved survival with transplantation. Extended criteria donor (ECD) organs are increasingly utilized to meet the demand for transplant livers. The purpose of this study is to evaluate the impact of ECD livers on post-transplant survival in patients with HCC, both inside and outside Milan criteria.



Records from 698 consecutive adult liver transplants from July 2001 to June 2006 were reviewed. Of these patients, 138 (19.8%) had HCC and 489 (70%) received ECD livers. Primary ECD criteria included: age ≥ 60, BMI ≥ 35, maximum AST or ALT > 500, maximum bilirubin > 2.0, peak serum sodium > 170, HBV/HCV/HTLV reactive, non-heart beating donor, cold ischemia time > 12 hours, ICU stay > 5 days, ≥ 3 pressors simultaneously, and extensive chronic alcohol abuse. Outcomes included 1- and 2-year survival and HCC recurrence. Kaplan-Meier estimates of survival time for ECD vs. standard donor (SD) groups were compared using the log-rank test. The simultaneous impact of MELD score, primary diagnosis, recipient age, transplant year and Milan status for patients in the two groups was evaluated by a Cox proportional hazards model.



Median follow-up for the entire population was 25.4 months from the date of transplantation.  Medican follow-up for survivors was 31.8 months.  Of the 138 patients, 31 (22.5%) have died: 10 (7%) died of cancer, 4 (3%) died of recurrent hepatitis C and liver failure, 7(5%) died of other or unknown causes.  There are 107 (77.5%) patients who are currently alive, 6 (4.3%) with and 101 (73.2%) without evidence of disease recurrence.  No patients were lost to follow-up.


The estimated mean survival from the date of transplant was 52.4 months for patients in the DS group and 54.8 months in patients receiving ECD (p=0.61 by unpaired t-test with Welch’s correction).  Overall actuarial survival at 1 year was 85% (ECD 83.6%, SD 87.5%), and 77% at 2-years (ECD 77.3%, SD 76.9%).



The use of extended criteria donor livers increases organ availability for patients with liver disease and provides acceptable survival in patients with HCC.  In this cohort of patients transplanted with HCC, there was not significant difference in overall survival between those receiving a standard donor liver and those receiving an ECD liver.  Additionally, tumor recurrence rates did not differ between the ECD and SD groups.  Thus, transplantation with ECD livers does not appear to impart any oncologic detriment for patients with HCC.  These results suggest that ECD livers represent a viable avenue for expanding the opportunity to offer transplant to patients with CCC, even those who are not typically considered acceptable candidates. 


There was no difference between the ECD and SD groups in tumor recurrence. Overall survival was also the same regardless of Milan criteria. These results suggest that ECD livers represent a viable avenue for expanding the opportunity to offer transplant to patients with HCC, even those who are not typically considered acceptable candidates.


Topic:  Liver Transplantation –General


S1738. Diabetes Mellitus Is An Independent Predictor Of Late Mortality Following Orthotopic Liver Transplantation. 

M. Lee; A. Kamal; A. Lapasaran; E. B. Keeffe; C. O. Esquivel; A. Ahmed.



Previous studies suggest that liver transplant patients with diabetes mellitus have increased risk of death up to 6 years following transplant, but these studies did not control for MELD score.



We studied our patient population to determine if diabetes mellitus was a predictor of late mortality independent of MELD score.



We conducted a retrospective analysis of all adult patients undergoing liver transplantation at Stanford University Medical Center between February 1995 and July 2006.



Of 530 patients identified, information regarding diabetes mellitus was available for 431. Patients with acute liver failure (n=17), undergoing kidney-liver transplant (n=28), and dying prior to discharge (n=51) were excluded.


Of the remaining 370 patients, diabetes mellitus was present in 62 (Table 1). Over a mean follow-up of 4.46 years, survival was 81% in the diabetic group and 94% among controls (Figure 1). In the diabetic group, the most common causes of death were unknown (30%), metastatic cancer (20%), and graft failure (20%); among non-diabetics, common causes of death were multiorgan failure (33%), gastrointestinal bleeding (20%), and metastatic cancer (20%).  Diabetes mellitus remained a significant predictor of death (HR 3.11, p = 0.01), even after controlling for MELD score, age, BMI and presence of HCV.



Diabetes mellitus is an independent risk factor for mortality following liver transplantation.  Future research is needed to study accelerated atherosclerosis in the setting of immune suppression among  diabetics and the effects of diabetes-related systemic metabolic derangements on allograft function as an explanation for this finding.


Demographic Characteristics



No diabetes

p value

Number of patients




Mean age (years)




Mean BMI (kg/m2)




Presence of HCV




Mean follow-up




Mean MELD score





Topic:  Liver Transplantation—Post


S1743. The use of old donors increases the risk of graft loss in the first year after liver transplantation because of non anastomotic bliliary strictures.

T. Serrano; A. Garcia-Gil; J. Arenas; Y. Ber; C. Valiente; R. Sainz.



The impact of donor age on liver transplantation has been analysed by several studies, but all of them are retrospective, and the results are contradictory.



To evaluate graft survival and complications of liver transplantation with old donors in the first year after transplantation.



Prospective analysis of 181 consecutive L liver transplantations performed between February 2000 and June 2005. Patients who died with normal liver function before 1 year after liver transplantation, patients with ABO incompatible donors, and those who were lost in the follow-up were excluded (n=29). liver transplantations were divided into two groups depending on donor age:


A.   Less than 60 years old (n=104);

B.    ≥60 years old (n=48).



During the follow-up period, 13 out of 48 grafts in the group of older donors were lost (27.1%), and 14 out of 104 (13.5%) were lost in the other group (OR 2.4; 95%CI: 1.06-5.58; p=0.04). The incidence of acute and chronic rejection, infection and arterial complications was similar in both groups, but biliary complications were higher in the older donor group (31.3% vs 14.4%, OR 2.7; 95%CI:1.2-6.1; p<0.05).


The incidence of anastomotic biliary strictures was similar in both groups (7.7% group A vs 8.3%), but the incidence of non-anastomotic biliary stenosis NABS was clearly higher in the older donor group (18.8% versus 5.8%; OR 3.8; 95%CI: 1.26-11.30; p<0.05).


The main cause of graft loss in the older donor group was NABS. In almost half of patients with NABS, no hepatic arterial complications were found. Protocol biopsies done at the end of the first year in 80% of HCV infected livers (n=34) showed that patients included in group B had more severe fibrosis (stage 3 or 4 ) than younger donor recipients (58.3% vs4.5%; OR=29.4; 95%CI: 2.9-296.5; p<0.001.


Graft survival 12 months after LT was higher in younger donors (86.5% vs 72.9%; p<0.05).



The use of grafts from donors ≥60 years increases the incidence of biliary complications, severity VCH reinfection and is related to a increase in graft loss in the first year after liver transplantation mainly because of NABS.


Topic:  Liver Transplantation - Post


S1758. Causes of Death Associated With Hepatitis B or Hepatitis C Virus Infections in a Long-Term Population-Based Cohort Study. 

H. Yang; C. Chen; C. Jen; U. H. Iloeje; J. Su; S. You.


Background and Aims:

Chronic infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) are well-documented risk factors for cirrhosis and hepatocellular carcinoma (HCC). We aimed to investigate mortality associated with the viruses in this study.



The mortality of this cohort was follow-up between Jan 1, 1991 and Dec 31, 2004. Mortality was ascertained via data linkage to the Taiwanese National Death Certification Registry, which has been shown to be complete and accurate. Mortality rates for all causes, liver cancer, chronic liver disease and cirrhosis and others were derived. Survival curves with stratification by HBV/HCV infection status were derived by the Kaplan-Meier method. Cox proportional hazards models were used to estimate multivariable-adjusted relative risks (RRadj) and 95% confidence intervals (CIs).



Among a total of 23,186 cohort members (290872.7 person-years of follow-up), the number (prevalence) of HBV, HCV, HBV/HCV co-infection and neither HBV nor HCV infections was 3,895 (16.8%), 1040 (4.5%), 215 (0.9%) and 18,036 (77.8%), respectively.


The all causes mortality per 100,000 person-years was 877.1, 1248.7, 1179.9, and 595.1 for HBV, HCV infections, HBV/HCV co-infection and neither HBV nor HCV infection, respectively (liver cancer mortality: 284.1, 257.6, 228.4, 12.3; mortality of chronic liver disease and cirrhosis: 85.0, 93.7, 152.2, 16.7; non-liver-related mortality: 508.0, 897.5, 799.3, 566.0).


Taking those with neither HBV nor HCV infection as referent, the RRadj (95% CI) of all cause mortality adjusted for gender, age, cigarette smoking and alcohol consumption was 1.7 (1.5-1.9), 1.8 (1.6-2.2), and 1.9 (1.3-2.6) for HBV, HCV infections, and HBV/HCV co-infection, respectively [liver cancer mortality: 25.2 (16.8-37.9), 19.6 (11.8-32.5), 17.4 (7.2-42.1); mortality of chronic liver disease and cirrhosis: 5.5 (3.5-8.6), 5.3 (2.8-10.2), 9.0 (3.2-25.1); non-liver-related mortality: 1.1 (0.9-1.2), 1.4 (1.1-1.7), 1.3 (0.9-2.0)]. Subjects infected with HCV only had significantly higher risk of dying from cerebrovascular disease and renal failure with RRadj (95% CI), 2.2 (1.4-3.6) and 2.9 (1.3-6.1), respectively.



HBV, HCV infections and HBV/HCV co-infection had elevated risk of liver-related mortality compared with neither HBV nor HCV infection. HCV infection may be associated with death from several extra-hepatic manifestations such as cerebrovascular disease and renal failure.


Hepatitis B:  Diagnostic Tools


S1765. Changes in Serum Alanine Aminotransferase (ALT) Level Using a Trajectory Model and Risk of Hepatocellular Carcinoma (HCC) in Chronic Hepatitis B (CHB): The R.E.V.E.A.L.-HBV Study. 

C. Chen; M. Lee; W. Lee; C. Jen; H. Yang; U. H. Iloeje; J. Su; S. Lu; S. You; C. Chen



Serum ALT is a marker of hepatocyte damage in chronic hepatitis. 




·        evaluate the relationship between ALT changes over time and HCC risk;

·        examine the baseline factors associated with ALT changes over time.



A subgroup of the R.E.V.E.A.L.–HBV cohort of HBsAg-seropositive and anti-HCV-seronegative participants, with ≥5 ALT measurements, was used in the analyses. The outcome was new liver cancer (HCC) cases.  We defined low, medium, and high ALT as <20 U/L, ≥20 U/L but <45 U/L, and ≥45 U/L, respectively. A semi-parametric group-based modeling was used to determine major classes of ALT trajectories. Associations between baseline risk factors and the ALT trajectories were examined using polytomous logistic regression. Cox proportional hazards modeling was used to analyze the associations between the ALT trajectory classes and HCC risk.



A total of 1712 subjects with 61 new HCC cases contributed 21,225 person-years of follow-up. Four ALT trajectory classes were identified:

·        class I persistently low (n=551);

·        class II low-to-medium (n=808);

·        class III high-to-medium (n=99);

·        class IV medium-to-high (n=254).


Of the baseline risk factors, gender, age, HBeAg status, serum HBV DNA levels, and alcohol consumption were significantly associated with the ALT trajectory. With class I subjects as the reference group, the adjusted hazard ratio [HRadj (95% CI)] of developing HCC was 4.0 (1.2-13.4) for class II subjects; 4.6 (1.1-18.9) for class III subjects; and 7.4 (2.1-25.9) for class IV subjects after adjustment for gender, age, HBeAg status, HBV DNA levels, cigarette smoking, and alcohol consumption. With HBV DNA <300 c/mL as reference, the HRadj (95% CI) of developing HCC associated with baseline HBV DNA level was 1.8 (0.5-7.4) for HBV DNA 300 to <104 c/mL; 4.0 (1.1-14.8) for HBV DNA ≥104 to <105 c/mL; 7.1 (2-25.6) for HBV DNA ≥105 to <106; and 9.6 (2.5-36.2) for HBV DNA ≥106 c/mL.



Serum ALT changes over time is a strong independent predictor of HCC. Baseline HBV DNA was a significant predictor of the ALT trajectory over time and remained an important risk factor for HCC development after adjusting for the ALT trajectories.


Topic:  Disease Progression---Metabolic


S2158. Prevalence and associated factors of nonalcoholic liver fatty disease and metabolic syndrome: results from a cross-sectional study . 

A. Colecchia; A. Vestito; E. Petracci; M. Bacchi-Reggiani; A. Morselli-Labate; A. Di Biase; G. Mazzella; F. Lodato; M. Montagnani; F. Pasqui; D. Festi


Nonalcoholic fatty liver disease ( NAFLD) and metabolic syndrome ( MS) are considered closely related diseases, having insulin resistance as common pathogenetic mechianism. A few studies, however, have simultaneously assessed NAFLD and MS prevalence and associated factors in a general population.



To evaluate by means of a cross-sectional study prevalence and associate factors of NAFLD and metabolic syndrome.


Material and Methods:

The cross sectional study was performed on a general population, aged 28-84 yrs; 1534 out of 1646 ( 93%) subjects agreed to participate to the study. All subjects underwent abdominal ultrasound (US), physical examination, fasting blood specimen collection, seven day dietetic diary. NAFLD was evaluated by US and metabolic syndrome was defined according to ATP III criteria (presence of 3, or more, of the following parameters: waist circumference, fasting glucose, HDL-cholesterol, triglycerides, blood pressure). Insulin resistance was evaluated using the triglycerides/HDL-Cholesterol ratio ( Tg/Hdl ratio) ( n.v.< 3.5).



479 out of 1534 (31.2%) subjects were excluded because they presented other liver diseases (391 alcohol, 20 HBV, 63 HCV and 5 autoimmune).


382 out of 1055 subjects ( 36.1%) ( males 57.8%, mean age: 52.1 ± 12.7) had NAFLD, while 240 out of 1055 ( 22.7%) subjects had metabolic syndrome ( males 45.8%,mean age 55.5 ± 12.6).


In NAFLD,  metabolic syndrome prevalence was 41.6% (159 out of 382 subjects); at multivariate analysis, associate factors resulted: sex male (OR:1.89), systolic hypertension (OR:1.9), hyperglicemia (OR:1.9), visceral obesity (OR:4.9), Tg/HDL ratio (OR:2.9), ALT (OR:2,5), gGT (OR:1.8). NAFLD was present in 66.2% (159 out 240 subjects) of metabolic syndrome  subjects: at multivariate analysis associated factors resulted: increasing age (OR:1.5); female sex (OR:1.05); fatty liver ( OR:5.22); Tg/Hdl ratio ( OR: 23.04).



The present study confirms the strong association between NAFLD and metabolic syndrome; although NAFLD prevalence is higher. Subjects with NAFLD had higher risk (OR: 13.5) to have metabolic syndrome than vice-versa (OR: 5.22); this observation suggest that NAFLD could play an early role in the development of metabolic syndrome. Further epidemiological and pathophysiological studies are needed to better define which is the killer or the victim.