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Background: Liver cirrhosis may lead to hepatocellular carcinoma (HCC), regardless of its cause. Genetic and/or environmental factors may modulate the risk of HCC. Mutations in the HFE gene are responsible [...]

Summary: Background: Liver fibrosis is often accompanied by steatosis, particularly in patients with non‐alcoholic fatty liver disease (NAFLD), and its non‐invasive characterisation is of utmost importance. Vibration‐controlled transient elastography is the non‐invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. Aim: To determine how to use CAP in interpreting liver stiffness measurements. Methods: This is a secondary analysis of data from an individual patient data meta‐analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology‐specific liver stiffness measurement cut‐offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. Results: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut‐offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity‐optimised cut‐offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity‐optimised cut‐offs for cirrhosis. Conclusions: Liver stiffness measurement values below aetiology‐specific cut‐offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut‐offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis. [ABSTRACT FROM AUTHOR]

Summary. A novel controlled attenuation parameter (CAP) has been developed for Fibroscan® to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan® and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S0: steatosis in <10% of hepatocytes, S1: 11-33%, S2: 34-66% and S3: 67-100%. Performances of CAP and liver stiffness were determined using receiver operating characteristic (ROC) curve analysis and cross-validated using the bootstrap method. The Obuchowski measure was used to assess overall accuracy of CAP and to differentiate between steatosis grades. In multivariate analysis, CAP was related to steatosis ( P < 10−15) independently of fibrosis stage (which was related to LSM). The areas under ROC curves using CAP to detect steatosis were 0.80 (95% CI, 0.75-0.84) for S ≥ S1, 0.86 (0.81-0.92) for S ≥ S2 and 0.88 (0.73-1) S = S3. CAP exhibited a good ability to differentiate steatosis grades (Obuchowski measure = 0.92). Performance of LSM for fibrosis assessment confirmed results from previous studies. CAP is a novel tool to assess the degree of steatosis and both fibrosis and steatosis can be evaluated noninvasively during the same procedure using Fibroscan®, in patients with CHC. [ABSTRACT FROM AUTHOR]

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.British Journal of Cancer (2006) 95, 1379–1383. doi:10.1038/sj.bjc.6603429 www.bjcancer.com Published online 24 October 2006 [ABSTRACT FROM AUTHOR]

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 kappa and lambda immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC. [ABSTRACT FROM AUTHOR]

Summary In Western countries, most of the patients with hepatocellular carcinoma (HCC) are not eligible for curative treatments. Intra-arterial treatments have a palliative effect that could lead to extensive tumour necrosis and therefore have been widely used. Arterial embolization, Lipiodol-targeted chemoembolization and intra-arterial injection of radioactive iodine mixed with Lipiodol provided promising results in terms of tumoral growth, but were also responsible for severe side-effects, particularly in patients with cirrhosis. Their influence on survival has been assessed by randomized trials with contradictory results. In patients with advanced cases, embolization alone has limited or no influence on survival, and chemoembolization provided a beneficial effect mostly in patients with viral liver diseases, without liver failure, and with an adequate portal flux. The effects of radioactive iodine either in the treatment of advanced cases or the prevention of recurrences after a curative treatment must be investigated further. [ABSTRACT FROM AUTHOR]

ABSTRACT- Hepatitis C virus (HCV) has been proposed to be a cofactor in the pathogenesis of cirrhosis in patients with chronic alcoholism. The demonstration of a different liver histological pattern in anti-HCV positive patients might provide additional evidence. We studied 164 patients with chronic alcoholism, and histologically proven cirrhosis. For all of them, serum samples were collected at the time of a liver biopsy and stored at -80°C. Testing for anti-HCV antibodies was done using the Ortho Diagnostic Systems Anti-HCV ELISA test. Only reproducible results were considered positive. A semi-quantitative assessment of seven histological parameters was made independently on liver biopsy samples. In the study group, 29 patients (18%) had anti-HCV antibodies. When compared with anti-HCV negative patients, both groups had similar ALT and AST seric activities. Anti-HCV positive patients had a greater score of mononuclear cells infiltrate (0.71±0.57 vs 0.41 ±0.52; p<0.05) and a lesser score of alcoholic hepatitis (0.19 ±0.57 vs 0.74 ±0.74; p<0.005). The scores for steatosis, perisinusoidal and perinodular fibrosis, and hepatocellular necrosis were similar in the two groups. In anti-HCV positive patients, with a clearly positive recombinant immunobinding assay (RIBA, Chiron-Ortho Diagnostic Systems), a greater score for hepatic necrosis and a lesser one for fibrosis were demonstrated. Among the seven patients with active cirrhosis, six were anti-HCV positive. Therefore, HCV is likely to play a role in the pathogenesis of liver damage in a few patients with alcoholic cirrhosis, especially, those with active cirrhosis. [ABSTRACT FROM AUTHOR]