It was known that mutations in the RT region were mainly related to nucleot(s)ide analogs resistance. Increasing studies indicated that RT mutations were related to advanced liver diseases (ALD) and had effects on HBV replication, but the distribution characteristics of mutations across RT region in the development of liver diseases and the effect of RT mutations on HBV replication were not fully clarified. HBV RT region was direct-sequenced in 1473 chronic HBV-infected patients. Mutation frequencies were analyzed to identify the specific mutations differing between groups classified by genotypes, loads of HBV DNA, or progression of liver diseases. In the range of rt145-rt290, rt145, rt221, rt222, rt267, and rt271 were the genotype-polymorphic sites, while rt238 was the genotype-specific sites. Mutations at rt163, rt173, rt180, rt181, rt184, rt191, rt199, and rt214 were more frequent among patients with C-genotype HBV, while those at rt220, rt225, rt226, rt269, and rt274 were more frequent among patients with B-genotype HBV. RtM204V/I could reduce the HBV DNA loads while rtQ/L267H/R could increase the HBV DNA loads. RtV214A/E/I (OR 3.94, 95% CI 1.09 to 14.26) was an independent risk factor for advanced liver diseases. In summary, the hotspots of mutations were different between B and C genotypes. Besides the effect on the S region, RT mutations had effects on HBV replication by other unknown ways. RtV214A/E/I was found to be an independent risk factor for ALD, suggesting that mutations at rt214 site could be used as a potential virological marker for the liver disease progression.

Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed.

Despite effective preventive primary prevention with vaccination, many people remain infected with hepatitis B virus (HBV) and suffer from its complications. Effective treatments such as interferon-based regimens and oral nucleoside/nucleotides have been developed over the last 30 years, but they are not perfect. Each of the treatments has its own merits, but none can eradicate HBV from the host. As a result, regular monitoring of the response during treatment and after treatment is required. The choice and monitoring of selected treatments, new potential therapeutic agents, and treatment options for drug resistance are discussed in this review.

Of the 2,635,000 new cancer cases (excluding non-melanoma skin cancers) occurring in the European Union (EU) in 2012, it is estimated that approximately 185,000 are related to infection with human papillomaviruses (HPVs), hepatitis B and C viruses (HBV and HCV), and Helicobacter pylori (H. pylori). Chronic infection with these agents can lead to cancers of the cervix uteri, liver, and stomach, respectively. Chronic infection with HCV can also lead to B-cell non-Hodgkin lymphoma. Human immunodeficiency virus (HIV) infection continues to be of major public health importance in several EU countries and increases cancer risk via HIV-induced immunosuppression. The fourth edition of the European Code Against Cancer presents recommendations on effective and safe preventive interventions in order to reduce the risk of infection-related cancers in EU citizens. Based on current available evidence, the fourth edition recommends that parents ensure the participation of their children in vaccination programs against HBV (for newborns) and HPV (for girls). In the 'Questions and Answers' (Q&As) section about vaccination and infections in the website for the European Code Against Cancer, individuals who are at risk of chronic HBV or HCV are advised to seek medical advice about testing and obtaining treatment when appropriate. Individuals most at risk of HIV are advised to consult their doctor or healthcare provider to access counselling and, if needed, testing and treatment without delay. Information about H. pylori testing and treatment is also provided as testing might currently be offered in some high-risk areas in Europe. The rationale and supporting evidence for the recommendations on vaccination in the European Code Against Cancer, and for the main recommendations on vaccination and infection in the Q&As, are explained in the present review.

About 80% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections especially in the setting of established cirrhosis or advanced fibrosis, making HCC prevention a major goal of antiviral therapy. HCC tumors are highly complex and heterogeneous resulting from the aberrant function of multiple molecular pathways. The roles of HCV or HBV in promoting HCC development are still either directly or indirectly are still speculative, but the evidence for both effects is compelling. In patients with chronic hepatitis viral infection, cirrhosis is not a prerequisite for tumorigenesis.

Liver cancer is one of the most common cancers. Hepatocellular carcinoma (HCC) represents > 90% of primary liver cancers and is a major global health problem today. Chronic hepatitis B virus (HBV) infection is associated with more than half of HCCs.

Long-term therapy with nucleos(t)ide analogues (NUCs) improves outcomes in HBV-infected patients by slowing the progression of liver disease. It is associated with improvements in histological and clinical outcomes, improved patient survival, reduced need for liver transplantation and improved liver function in patients with decompensated liver disease. This review highlights the results of previous studies conducted on HCC prevention with long-term NUC therapy. Studies include the use of all available drugs in different clinical scenarios, and the comparison between treated and untreated patients.

NUCs have been studied extensively in HCC prevention. A comprehensive review of the literature has shown that they can be safely and effectively used for this purpose. Despite some discrepancies between studies, most of the evidence favors using NUC therapy for HCC prevention.

Hepatocellular carcinoma (HCC) is a frequent, long term complication of chronic infection with hepatitis B virus (HBV) with an annual incidence ranging from 2 to 5%, often independent from the histological stage of underlying liver disease and serological status. Nevertheless, HCC is more often seen in older patients in whom HBV has been asserting its pro-oncogenic properties through both indirect and direct mechanisms. In Europe, HBV-related HCC is associated with cirrhosis in most patients, whereas this is not true in Asia and Africa where the tumour is also common among carriers with mild hepatic fibrosis, probably because of the coexistence of environmental co-carcinogens (aflatoxin) and long standing infection that is often acquired perinatally. Since hepatitis B-related carcinogenesis develops independently of the onset of cirrhosis, antiviral treatments such as nucleo(t)side analogues (NAs) that may result in the regression of fibrosis, prevent clinical decompensation and variceal bleeding, often fail to prevent HCC. Studies enrolling patients treated with lamivudine or rescued with adefovir, i.e. regimens characterized by limited potency and a low to moderate genetic barrier, have clearly been shown to help prevent HCC in patients with chronic hepatitis but not in those with cirrhosis, and in general not in patients that cannot achieve a sustained virological response. More potent anti-HBV drugs, such as entecavir and tenofovir, have been shown to improve the prevention of HCC in responders with cirrhosis, although HCC may still occur even in low risk patients. To attenuate HCC related outcomes, HBV replication must permanently be suppressed and HCC surveillance by abdominal ultrasound should be maintained even in responder patients.

The hepatitis B virus (HBV) plays a dominant role in the 749,000 new cases and 692,000 deaths related to hepatocellular carcinoma (HCC) that are estimated to occur each year worldwide. Chronic infection with HBV is responsible for 60% of HCCs in Asia and Africa and at least 20% of the tumors in Europe, Japan, and the United States. This article discusses the pathogenic role of HBV and the risk of HCC. Tumors almost invariably develop in the context of chronic hepatitis or cirrhosis, which makes early diagnosis the only practical approach to improve prognosis. The treatment options are also discussed.

Chronic hepatitis B (CHB) infection is the major cause of hepatocellular carcinoma (HCC). Primary prevention of hepatitis B infection by vaccination is effective in reducing the incidence of HCC. In persons with CHB infection, the two accepted treatment modalities are interferon alpha (IFN-α) given subcutaneously for a limited period and nucleoside/nucleotide analogs given orally on a long-term basis. These treatments are effective in suppressing viral activity and improving disease markers in short-term studies. The long-term effect on the development of liver cancers with these two forms of treatment appears to be different. However, there are no studies directly comparing IFN-α and nucleoside/nucleotide analogs. Comparisons across studies are inevitably limited by differences in the baseline characteristics of the study cohorts. Long-term follow-up studies of IFN-α therapy show inconsistent results. The beneficial effect in reducing the development of liver cancer is observed mainly in treatment responders who have preexisting cirrhosis of the liver. The long-term studies of lamivudine (and adefovir) show a consistent reduction in the development of liver cancers in patients with, and without, cirrhosis. This beneficial effect is blunted by the development of resistance. The effects of the newer nucleoside/nucleotide analogs, with higher potency and minimal risk of resistance development, are, as yet, unknown.