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One of them comes from post-hoc analysis of the registration trial of tenofovir, which was reported as an abstract. In this report by Sievert et al[49], investigators included 641 patients with CHB receiving open-label tenofovir therapy for 6 years and compared HCC incidence with the estimated risk calculated Ribonucleotide reductase by REACH-B model[50]. They reported that 14 tenofovir-treated patients (6 of them were cirrhotic) developed HCC during the follow-up and the incidence of HCC decreased with a standardized incidence ratio of 0.45 (95%CI: 0.23-0.91) compared to the estimated risk. Despite the low number of HCC cases in this study, they concluded by emphasizing continued surveillance for CHB patients receiving long term oral antiviral treatment. There are several meta-analyses or systematic reviews that confirmed the beneficial effects of NAs in the prevention of HCC in CHB. In a systematic review by Papatheodoridis Cisplatin chemical structure et al[51], 21 studies were reviewed and 3 of them which were of high quality and included untreated controls. In the pooled analysis of 3 studies, HCC was detected significantly less frequently in treated than in untreated patients (2.8% vs 6.4%, respectively, P = 0.003). Interestingly, they found that incidence of HCC was significantly higher in untreated patients even when compared to treated patients with virological breakthroughs or no response. Similarly, other meta-analyses confirmed these results regarding the influence of NAs on HCC risk (Table ?(Table22)[52-54]. Table 2 Systematic review and meta-analyses investigating hepatocellular carcinoma risk selleck chemicals reduction in patients receiving nucleos(t)ide analogues vs untreated controls Although it is evident to say that antiviral therapy decrease HBV-related HCC incidence when compared with the natural course of the disease, there are sufficient data showing that antiviral therapy does not eliminate the HCC risk completely, even in non-cirrhotic patients with sustained virological suppression. Papatheodoridis et al[55] included 818 patients with HBeAg-negative CHB treated with NAs in a retrospective study investigating HCC incidence. All patients were treated with NAs starting with lamivudine monotherapy, and during a median follow-up of 4.7 years 49 patients (6%) eventually developed HCC. The study demonstrated a trend for lower cumulative HCC incidence in CHB patients with virological on-therapy remission (P = 0.076), which was defined as maintained undetectable HBV-DNA (