Although chronic HBV infection is the leading cause of chronic liver disease and death worldwide, there are substantial differences in its clinical courses regarding prevalence, mode of transmission, characteristics of each phase, responses to antiviral therapy, and development of cirrhosis and hepatocellular carcinoma, according to geographical areas (Asia versus Western Europe and North America versus Africa). Furthermore, the clinical course in infected individuals depends on a complex interplay among various factors including viral, host, environmental and other factors. Recently, understanding of molecular characteristics of the prevailing HBV genotypes, frequently accompanied mutations and their clinical implications might explain these geographical differences more pertinently. Hence, in this article, we review the global epidemiology and the natural history of HBV infection, with emphasis on summarizing the different HBV genotypes according to regions.

Background and Aims The modified PAGE‐B (mPAGE‐B) score comprising age, gender, platelet count and albumin was recently proposed to predict hepatocellular carcinoma (HCC) risk among chronic hepatitis B (CHB) patients undergoing antivirals. Here, in the independent cohort, we externally validated the predictive performance of the mPAGE‐B score and compared it with those of conventional HCC prediction models. Methods We consecutively recruited CHB patients treated with lamivudine, entecavir or tenofovir as the first‐line antiviral regimen. Patients with decompensated cirrhosis or HCC at baseline were excluded. Predictive performances of the mPAGE‐B score and other models were assessed with comparison. Results Among 1330 patients, 9.6% developed HCC during follow‐up. The mPAGE‐B score provided the highest Harrell's c‐index (0.769), followed by the GAG‐HCC (0.751), PAGE (0.744), REACH‐B (0.686) and CU‐HCC (0.618) scores. The mPAGE‐B score showed the similar performance to the PAGE‐B and GAG‐HCC scores and the better performance than the REACH‐B and CU‐HCC scores. Cumulative HCC probabilities at 5‐ and 7‐years were 0.0% and 0.0% in low‐risk group (mPAGE‐B score ≤ 8), 6.1% and 10.8% in intermediate‐risk group (mPAGE‐B score 9‐12) and 18.7% and 26.7% in high‐risk group (mPAGE‐B score ≥ 13) respectively (both P < 0.001 between adjacent two groups). C‐indices of the mPAGE‐B score were 0.785 and 0.724 among subgroups treated with entecavir or tenofovir (n = 1011) and with lamivudine (n = 319), respectively, which are overall similar to those of the PAGE‐B score. Conclusion The mPAGE‐B score showed acceptable predictive performances. Compared to the PAGE‐B score, addition of albumin as a constituent provided the marginal benefit.

Chronic hepatitis B (CHB) accounts for approximately 50% of the underlying etiologies for the development of hepatocellular carcinoma (HCC) worldwide. We reviewed the primary, secondary, and tertiary measures for the prevention of HCC in CHB patients. First, the most effective method is preventing the acquisition of CHB through global vaccination of infants. However, in patients already chronically infected, antiviral treatment using interferon or nucleoside analogs can prevent disease progression to cirrhosis or HCC. Studies have found viral replications indicated by a HBV DNA level to be a strong predictor for cirrhosis and HCC, irrespective of other viral and biochemical factors. Additionally, periodic surveillance using ultrasonography and serum α-fetoprotein every 3–6 months for earlier detection of HCC is also important so that curative treatments can be used. Once HCC occurs, hepatic resection is the mainstay of curative treatments. To prevent tumor recurrence after resection, adjuvant interferon treatments have been tried with promising results based on the assumption that they not only suppress viral activity but also have tumoricidal, antiangiogenetic, and antiproliferative effects. Using nucleoside analogs also has its rationale for preventing de novo tumor development in remnant liver, considering that viral replications are a strong risk factor for HCC. Optimal preventive plans should be further investigated in future studies.

Backgrounds/Aims Monitoring fibrosis is mandatory for detailed prognostification in patients with chronic liver disease. We developed optimized cut‐offs for liver stiffness (LS) values, based on the histological subclassification of cirrhosis, and investigated whether early on‐treatment changes in LS values can predict long‐term prognosis in patients with hepatitis B virus (HBV)‐related advanced liver fibrosis receiving antiviral therapy. Methods Between 2005 and 2008, 103 patients with F3 or F4 fibrosis on liver biopsy were enrolled prospectively. Cirrhosis was subclassified into three groups (F4A, F4B and F4C) according to Laennec system. The primary end‐point was occurrence of liver‐related event (LRE), including decompensation, hepatocellular carcinoma and liver‐related death. Results Suggested LS cut‐offs for predicting F4B‐FC (vs. F3‐F4A) and F4C (vs. F3‐F4B) were 11.6 and 18.2 kPa respectively. As proportions of patients with LRE occurrence increased according to histological subclassifications stage F3‐4A vs. F4B‐4C (7.4% vs. 17.1%) and stage F3‐4B vs. F4C (13.8% vs. 18.8%), they also increased according to LS cut‐off value of 11.6 kPa (5.9% vs. 23.1%) and 18.2 kPa (9.8% vs. 33.3%) respectively (all P < 0.05). Similarly, according to stratified LS values (<11.6, 11.6–18.2 and ≥18.2 kPa), overall incidence of LREs and each constituent event increased significantly (all P < 0.05). In addition, the observed changes in LS values between baseline and 6 months of follow‐up showed significant correlations with LRE development. Conclusions Stratified LS values based on Laennec system and dynamic changes in LS values on follow‐up may be helpful in assessing risk of LREs in subjects with HBV‐related advanced liver fibrosis receiving antiviral therapy.