Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis

Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a ‘blind' test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73–99%) and 86% specificity (95% CI 65–95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (P<0.001) and were identified as κ and λ immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC

Preclinical and post-treatment changes in the HCC-associated serum proteome

SELDI-based proteomic profiling of body fluids is currently in widespread use for cancer biomarker discovery. We have successfully used this technology for the diagnosis of hepatocellular carcinoma (HCC) in hepatitis C patients and now report its application to serial serum samples from 37 hepatitis C patients before development of HCC, with HCC and following radiofrequency ablation of the tumour. As with alpha-fetoprotein, an accepted biomarker for HCC, we hypothesised that HCC-associated proteomic features would ‘return to normal' following successful treatment and the primary aim of our study was to test this hypothesis. Several SELDI peaks that changed significantly during HCC development were detected but they did not reverse following treatment. These data may be interpreted to suggest that the characteristic SELDI profile is not linearly related to tumour burden but may result from the progression of underlying liver disease or from the emergence of precancerous lesions. β2-Microglobulin, a protein previously reported to be markedly elevated in patients with HCV related HCC, was also the most significantly HCC associated proteomic feature (m/z 11720) in this study

No-Touch Multi-bipolar Radiofrequency Ablation for the Treatment of Subcapsular Hepatocellular Carcinoma ≤ 5 cm Not Puncturable via the Non-tumorous Liver Parenchyma.

The percutaneous ablation of subcapsular hepatocellular carcinoma (S-HCC) may involve a risk of complications such as hemorrhage and tumor seeding, mainly linked to the direct tumor puncture often inevitable with mono-applicator ablation devices. The purpose of this study was to assess the efficacy and safety of no-touch multi-bipolar radiofrequency ablation (NTMBP-RFA) for the treatment of S-HCC ≤ 5 cm not puncturable via the non-tumorous liver parenchyma. Between September 2007 and December 2014, 58 consecutive patients (median age: 63 years [46-86], nine females) with 59 S-HCC ≤ 5 cm (median diameter: 25 mm [10-50 mm]), not puncturable via the non-tumorous liver parenchyma, were treated with NTMBP-RFA. Response and follow-up were assessed by CT or MRI. Complications were graded using the Cardiovascular and Interventional Radiological Society of Europe classification. Overall local tumor progression (OLTP)-free survival was assessed using the Kaplan-Meier method. A Cox proportional model evaluated the factors associated with OLTP. Signs of peritoneal or parietal tumor seeding were noted during follow-up imaging studies. A complete ablation was achieved in 57/58 patients (98.3%) after one (n = 51) or two (n = 6) procedures. Three patients (5.2%) experienced complications (sepsis, cirrhosis decompensation; CIRSE grade 2 or 3). After a median follow-up period of 30.5 months [1-97], no patients had tumor seeding. The 1, 2 and 3-year OLTP-free survival rates were 98%, 94% and 91%, respectively. No factors were associated with OLTP. NTMBP-RFA is a safe and effective treatment for S-HCC not puncturable via the non-tumorous liver parenchyma