Insulin resistance measured by HOMA-IR, regardless of the presence of diabetes, is significantly associated with HCC development in patients with chronic HCV infection.

Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age-and sex-matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow-up. A panel of ten cancer-associated miRNAs was analyzed by quantitative real-time reverse-transcription polymerase chain reaction. Serum levels of miR-16, miR-122, miR-221, let-7b and miR-15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR-122, miR-let-7b and miR-15b levels increased significantly (p 5 0.046, 0.043 and 0.044, respectively). As a single marker, a-fetoprotein (AFP) and miR-122 as well as let-7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let-7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p 5 0.001). In conclusion, miR-122 and let-7b, which are upregulated in the serum of early-HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients.Hepatocellular carcinoma (HCC) is the sixth most common malignancy, and the third leading cause of cancer-related death in the world.1 Approximately 80-90% of patients with HCC have the underlying viral etiologies. 2-4 From a global perspective, the most important risk factor for HCC is chronic hepatitis B virus (HBV) infection, which is highly endemic in many Asian countries including Taiwan. 2-5 The overall 5-year survival rate is 5-9% from the time of clinical diagnosis of HCC, and the dismal prognosis is largely caused by late detection of the tumors. 6,7 Therefore, early detection of HCC at a curative stage offers the best chance of survival for these patients. Currently, diagnosis of HCC is based on imaging studies and sometimes verified by biopsy results.8 Advances in magnetic resonance imaging (MRI) and computed tomography (CT) have greatly improved imaging of focal hypervascular masses consistent with HCC, but these procedures are costly and not suitable for daily practice. Thus, sensitive and specific cancer biomarkers are essential for early detection and diagnosis of HCC as well as for developing preventive screening. Laboratory analyses including serum a-fetoprotein (AFP) and des-gamma carboxyprothrombin levels have long been used as HCC biomarkers. However, the accuracy of AFP is modest (sensitivity: 39-65%; specificity: 76-94%) and onethird of cases of early-stage HCC are missed using AFP analysis. 9 Also, serum AFP levels are probably false positive in patients with benign liver diseases, such as hepatitis and cirrhosis.10

Compared with 12-month interval, US surveillance at 4-month interval detected more patients with HCC ≤ 2 cm who were in BCLC very-early stage and were fit for curative treatments. Up to 4-year follow-up, however, the overall survival was not different.

This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.