We previously reported encouraging results of down-staging of hepatocellular carcinoma (HCC) to meet conventional T2 criteria (one lesion 2–5 cm or two to three lesions <3 cm) for orthotopic liver transplantation (OLT) in 30 patients as a test of concept. In this ongoing prospective study, we analyzed longer-term outcome data on HCC down-staging in a larger cohort of 61 patients with tumor stage exceedingT2criteriawhowere enrolled between June 2002 and January 2007. Eligibility criteria for down-staging included: (1) one lesion >5 cm and up to 8 cm; (2) two to three lesions with at least one lesion >3 cm and not exceeding 5 cm, with total tumor diameter up to 8 cm; or (3) four to five lesions with none >3 cm, with total tumor diameter up to 8 cm. A minimum observation period of 3 months after down-staging was required before OLT. Tumor down-staging was successful in 43 patients (70.5%). Thirty-five patients (57.4%) had received OLT, including two who had undergone live-donor liver transplantation. Treatment failure was observed in 18 patients (29.5%), primarily due to tumor progression. In the explant of 35 patients who underwent OLT, 13 had complete tumor necrosis, 17 met T2 criteria, and five exceeded T2 criteria. The Kaplan-Meier intention-to-treat survival at 1 and 4 years after down-staging were 87.5% and 69.3%, respectively. The 1-year and 4-year posttransplantation survival rates were 96.2% and 92.1%, respectively. No patient had HCC recurrence after a median posttransplantation follow-up of 25 months. The only factor predicting treatment failure was pretreatment alpha-fetoprotein > 1,000 ng/mL. Conclusion Successful down-staging of HCC can be achieved in the majority of carefully selected patients and is associated with excellent posttransplantation outcome.

Background & Aims-Reports of complications among adult right hepatic lobe donors have been limited to single centers. The rate and severity of complications in living donors were investigated in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL).

Patients considering living donor liver transplantation (LDLT) need to know the risk and severity of complications compared to deceased donor liver transplantation (DDLT). One aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was to examine recipient complications following these procedures. Medical records of DDLT or LDLT recipients who had a living donor evaluated at the nine A2ALL centers between 1998 and 2003 were reviewed. Among 384 LDLT and 216 DDLT, at least one complication occurred after 82.8% of LDLT and 78.2% of DDLT (p = 0.17). There was a median of two complications after DDLT and three after LDLT. Complications that occurred at a higher rate (p < 0.05) after LDLT included biliary leak (31.8% vs. 10.2%), unplanned reexploration (26.2% vs. 17.1%), hepatic artery thrombosis (6.5% vs. 2.3%) and portal vein thrombosis (2.9% vs. 0.0%). There were more complications leading to retransplantation or death (Clavien grade 4) after LDLT versus DDLT (15.9% vs. 9.3%, p = 0.023). Many complications occurred more commonly during early center experience; the odds of grade 4 complications were more than twofold higher when centers had performed ≤20 LDLT (vs. >40). In summary, complication rates were higher after LDLT versus DDLT, but declined with center experience to levels comparable to DDLT.

The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) remains controversial. To understand the transition from benign to malignant, we studied the gene expression patterns in liver tissues at different stages, including normal, cirrhosis, and different HCC stages. We studied 108 liver tissue samples obtained from 88 distinct patients (41 HCV-cirrhotic tissues, 17 HCV-cirrhotic tissues from patients with HCC, and 47 HCV-HCC tissues). Differentially expressed genes (DEG) were studied by use of high-density oligonucleotide arrays. Among probe sets identified as differentially expressed via the F test, all pairwise comparisons were performed. Cirrhotic tissues with and without concomitant HCC were further evaluated, and a classifier was used to predict whether the tissue type was associated with HCC. Differential expression profiles were analyzed using Interaction Networks and Functional Analysis. Characteristic gene signatures were identified when normal tissue was compared with cirrhosis, cirrhosis with early HCC, and normal with HCC. Pathway analysis classified the cellular and biological functions of the DEG as related to cellular growth and proliferation, cell death and inflammatory disease in cirrhosis; cell death, cell cycle, DNA replication, and immune response in early HCCs; and cell death, cell growth and proliferation, cell cycle, and DNA repair in advanced HCCs. Characteristic gene signatures were identified at different stages of HCV-HCC progression. A set of genes were identified to predict whether the cirrhotic tissue was associated with HCC.

Improvements in human immunodeficiency virus (HIV)-associated mortality make it difficult to deny transplantation based upon futility. Outcomes in the current management era are unknown. This is a prospective series of liver or kidney transplant recipients with stable HIV disease. Eleven liver and 18 kidney transplant recipients were followed for a median of 3.4 years (IQR [interquartile range] 2.9-4.9). One-and 3-year liver recipients' survival was 91% and 64%, respectively; kidney recipients' survival was 94%. One-and 3-year liver graft survival was 82% and 64%, respectively; kidney graft survival was 83%. Kidney patient and graft survival were similar to the general transplant population, while liver survival was similar to the older population, based on 1999-2004 transplants in the national database. CD4+ T-cell counts and HIV RNA levels were stable; and there were two opportunistic infections (OI). The 1-and 3-year cumulative incidence (95% confidence intervals [CI]) of rejection episodes for kidney recipients was 52% (28-75%) and 70% (48-92%), respectively. Two-thirds of hepatitis C virus (HCV)-infected patients, but no patient with hepatitis B virus (HBV) infection, recurred. Good transplant and HIV-related outcomes among kidney transplant recipients, and reasonable outcomes among liver recipients suggest that transplantation is an option for selected HIV-infected patients cared for at centers with adequate expertise.