Limited evidence is available on predictors of medical resource utilization (MRU) and related direct costs, especially in treatment-experienced patients infected with genotype 1 hepatitis C virus (HCV). This study aimed at investigating patient and treatment characteristics that predict MRU and related non-drug costs in treatment-experienced patients with chronic hepatitis C (CHC) treated with simeprevir (SMV) or telapravir (TVR) in combination with pegylated interferon and ribavirin (PegIFN/R).

A total of 709 patients who completed the 72-week ATTAIN trial were included in the study. Cost data were analysed from the UK NHS perspective. Descriptive statistics and regression analyses were used to determine patterns and predictors of total MRU-related costs associated with SMV/PegIFN/R and TVR/PegIFN/R.

Independent predictors for total MRU-related costs were age, region and the following interaction terms: (1) gender × F3–F4 METAVIR score × baseline viral load (BLVL), (2) body mass index (BMI) × F3–F4 METAVIR score × prior response to PegIFN/R and (3) gender × achievement of SVR at 12 weeks (SVR12) × BLVL. A F3–F4 METAVIR score was a stronger predictor of total MRU-related costs than SVR12. Predictors of adverse events included older age, female gender, low BMI, TVR/PegIFN/R and SVR12. Wilcoxon rank sum test revealed comparable total MRU-related costs between SMV/PegIFN/R and TVR/PegIFN/R.

To the best of our knowledge, this study is the first to describe the relationship between commonly admitted predictors of MRU-related costs and their joint effect on total MRU-related costs in treatment-experienced patients with CHC. The identified predictors of MRU-related costs suggest that significant treatment costs can be avoided by starting treatment early before the disease progresses. Furthermore, adverse events seem to be the most important factor to take into consideration for the choice of treatment, especially when therapeutic options are associated with similar levels of medical resource utilization and associated costs.

The online version of this article (doi:10.1007/s40268-015-0109-5) contains supplementary material, which is available to authorized users.

• Hepatocellular carcinoma
• Immunosuppression
• Liver transplantation
• Radiofrequency ablation
• Recurrence
• Resection
• Stereotactic body radiation therapy
• Targeted therapy
• Transarterial chemoembolization
• Transarterial radioembolization

Several microRNAs (miRNAs) are associated with the molecular pathogenesis of hepatocellular carcinoma (HCC). However, previous studies analyzing the dysregulation of miRNAs in HCC show heterogeneous results. We hypothesized that part of this heterogeneity might be attributable to variations of miRNA expression deriving from the HCC capsule or the fibrotic septa within the peritumoral tissue used as controls. Tissue from surgically resected hepatitis C–associated HCC from six well-matched patients was microdissected using laser microdissection and pressure catapulting technique. Four distinct histologic compartments were isolated: tumor parenchyma (TP), fibrous capsule of the tumor (TC), tumor-adjacent liver parenchyma (LP), and cirrhotic septa of the tumor-adjacent liver (LC). MiRNA expression profiling analysis of 1105 mature miRNAs and precursors was performed using miRNA microarray. Principal component analysis and consecutive pairwise supervised comparisons demonstrated distinct patterns of expressed miRNAs not only for TP versus LP (e.g., intratumoral down-regulation of miR-214, miR-199a, miR-146a, and miR-125a; P< .05) but also for TC versus LC (including down-regulation within TC of miR-126, miR-99a/100, miR-26a, and miR-125b; P< .05). The tumor capsule therefore demonstrates a tumor-like phenotype with down-regulation of well-known tumor-suppressive miRNAs. Variations of co-analyzed fibrotic tissue within the tumor or in controls may have profound influence on miRNA expression analyses in HCC. Several miRNAs, which are proposed to be HCC specific, may indeed be rather associated to the tumor capsule. As miRNAs evolve to be important biomarkers in liver tumors, the presented data have important translational implications on diagnostics and treatment in patients with HCC.

• AFP
• diagnosis
• dickkopfs
• hepatocellular carcinoma
• prognosis

• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Hepatectomy
• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Risk Factors
• Tumor Burden

The incidence of hepatocellular carcinoma (HCC) in Japan has still been increasing. The aim of the present study was to analyze the epidemiological trend of HCC in the western area of Japan, Kyushu.

A total of 10,010 patients with HCC diagnosed between 1996 and 2008 in the Liver Cancer study group of Kyushu (LCSK), were recruited for this study. Cohorts of patients with HCC were categorized into five year intervals. The etiology of HCC was categorized to four groups as follows; B: HBsAg positive, HCV-RNA negative, C: HCV-RNA positive, HBsAg negative, B+C: both of HBsAg and HCV-RNA positive, nonBC: both of HBsAg and HCV-RNA negative.

B was 14.8% (1,485 of 10,010), whereas 68.1% (6,819 of 10,010) had C, and 1.4% (140 of 10,010) had HCC associated with both viruses. The remaining 1,566 patients (15.6%) did not associate with both viruses.

Cohorts of patients with HCC were divided into six-year intervals (1996–2001 and 2002–2007). The ratio of C cases decreased from 73.1% in 1996–2001 to 64.9% in 2002–2007. On the other hand, B and -nonBC cases increased significantly from 13.9% and 11.3% in 1996–2001 to 16.2% and 17.6% in 2002–2007, respectively.

The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased after 2001 in Kyushu area. This change was due to the increase in the number and proportion of the HCC not only nonBC patients but also B patients.

• Adult
• Aged
• Female
• Genome, Viral
• Hepacivirus/drug effects
• Hepacivirus/genetics
• Hepacivirus/isolation & purification
• Hepatitis C, Chronic/virology
• Humans
• Interferons/pharmacology
• Male
• Middle Aged
• Mutation
• Polymerase Chain Reaction/methods
• RNA, Viral/genetics
• RNA, Viral/isolation & purification
• Transition Temperature

AIM: To determine, for hepatocellular carcinoma (HCC), the patient demographic profile and costs of their admissions to the hospitals of the Portuguese National Health System from 1993 to 2005.

METHODS: The National Registry (ICD-9CM, Inter-national Classification of Diseases, 155.0) provided data from the 97 Hospitals in Portugal.

RESULTS: We studied 7932 admissions that progres-sively rose from 292 in 1993 to 834 in 2005, having a male predominance of 78% (6130/7932). The global rate of hospital admissions for HCC rose from 3.1/10⁵ in 1993 to 8.3/10⁵ in 2005. The average length of stay decreased from 17.5 ± 17.9 d in 1993 to 9.3 ± 10.4 d in 2005, P < 0.001. The average hospital mortality for HCC remained high over these years, 22.3% in 1993 and 26.7% in 2005. Nationally, hospital costs (in Euros - €) rose in all variables studied: overall costs from €533 000 in 1993, to €4 629 000 in 2005, cost per day of stay from €105 in 1993, to €597 in 2005, average cost of each admission from €1828 in 1993, to €5550 in 2005. In 2005, 1.8% (15/834) of hospital admissions for HCC were related to liver transplant, and responsible for a cost of about €1.5 million, corresponding to one third of the overall costs for HCC admissions in that same year.

CONCLUSION: From 1993 to 2005 hospital admissions in Portugal for HCC tripled. Overall costs for these admissions increased 9 times, with all variables related to cost analysis rising accordingly. Liver transplant, indicated in a small group of patients, showed a disproportionate increase in costs.

• Hepatocellular carcinoma
• Hospitalization
• Length of stay
• Disease-related group cost analysis
• Hospital mortality

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Hepatocellular/economics
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/therapy
• Child
• Child, Preschool
• Costs and Cost Analysis
• Female
• Hospital Costs/statistics & numerical data
• Hospital Mortality
• Humans
• Infant
• Infant, Newborn
• Length of Stay/economics
• Length of Stay/statistics & numerical data
• Liver Neoplasms/economics
• Liver Neoplasms/epidemiology
• Liver Neoplasms/therapy
• Liver Transplantation/economics
• Liver Transplantation/statistics & numerical data
• Male
• Middle Aged
• Patient Admission/economics
• Patient Admission/statistics & numerical data
• Portugal/epidemiology
• Registries