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Anti-viral therapy in chronic hepatitis B (CHB) is associated with a reduced risk of hepatocellular carcinoma (HCC) primary described in patients with cirrhosis.To examine the effects of treatment on HCC incidence in CHB with and without cirrhosis, after adjustment for background risks.A total of 2255 CHB patients from a US cohort (973 received anti-viral therapy) and 3653 patients from the community-based Taiwanese REVEAL-HBV study, none of whom received treatment. We used Cox proportional hazard models to calculate the risk of developing HCC after adjustment with the previously validated REACH-B risk score.We found 273 incident cases of HCC. After adjustment, therapy lowered the risk of HCC development in the US treated cohort when compared to the US untreated cohort (HR 0.31; 95% CI: 0.15-0.66; P = 0.002). HCC risk reduction was also confirmed when compared to the REVEAL cohort (HR 0.22; 95% CI: 0.12-0.40; P0.001). Each REACH-B point was associated with a 53% increased risk of HCC (HR 1.53; 95% CI 1.46-1.59; P0.001). We found a significant statistical reduction in HCC incidence with therapy regardless of gender, age, cirrhosis status, HBeAg serology, alanine aminotransferase level, REACH-B score or treatment medication. Therapy was beneficial to those with mildly- to moderately elevated HBV DNA levels (2000 IU/mL) and of even greater benefit to those with levels200 000 IU/mL.After adjustment for background risk, anti-viral therapy was associated with a significant reduction in HCC incidence in both community and real-life clinical cohorts, including in those patients previously thought to be at low risk.

Chronic hepatitis B (CHB) is a dynamic disease, therefore patients initially ineligible for treatment, based on current guidelines, often become eligible at some point during their follow-up evaluation. We investigated the reasons for this change and developed a timeline for treatment eligibility for this population.We performed a retrospective cohort study of 245 consecutive treatment-naive, community-based patients with CHB who were not eligible for treatment when they first presented, from March 2007 through June 2010 (mean age, 44 y, almost all Asian). The patients were followed up for a median period of 26 months, receiving standard laboratory tests. They were treated according to US panel 2008 and American Association for Liver Disease (AASLD) 2009 guidelines.Fifty-four patients (22%) became eligible for treatment during the follow-up period; most of these (n = 47; 87%) were based on only the US Panel algorithm and the rest were based on AASLD guidelines (n = 7; 13%). Six percent of patients met the treatment criteria at 1 year, 18% at 2 years, and 29% at 3 years. Among hepatitis B e antigen-positive patients with levels of hepatitis B virus (HBV) DNA greater than 3 log IU/mL at baseline, 11% met treatment criteria at 1 year, 52% at 2 years, and 80% at 3 years. Based on Cox multivariate analysis, which included age; sex; and levels of hepatitis B e antigen, alanine aminotransferase, and HBV DNA, an increase in HBV DNA level was the only factor from the US panel associated with treatment eligibility (hazard ratio, 1.43; P.001), and an increase in alanine aminotransferase was the only factor associated with treatment eligibility from the AASLD guidelines (hazard ratio, 1.03; P = .001).Although most patients with CHB who initially are not eligible for treatment remain ineligible, almost 30% become eligible within 3 years. These findings indicate the importance of carefully following disease status in patients with CHB.

For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels. We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2 × ULN vs

G A A b st ra ct s CI = 19%-27%) for patients receiving only supportive care, 39% (95% CI = 32%-46%) for those receiving liver-directed palliative therapy, 61% (95%CI = 51%-70%) for those undergoing partial hepatectomy, and 77% (95% CI = 71%-82%) for those having a liver transplantation. In multivariate analysis (Table), independent predictors for improved survival were non-White/non-Black race, palliative as well as surgical treatment. Independent predictors for poorer survival were age older than 65 and Black race (compared toWhites). Conclusions: In spite of improved opportunity for both effective palliative and curative therapies in the recent years, almost half of patients meeting Milan criteria are still not undergoing any therapy. In addition to assessing the efficacy and survival impact of current therapies, it is also important to focus on why so many patients diagnosed with HCC are not undergoing any treatment and reasons for continued existence of racial disparities. Early diagnosis through better screening protocols together with patient and physician education is crucial to achieve better outcomes. Multivariate Cox Proportional Hazards Model Assessing Factors Associated with Survival

Background/Aims: Hepatitis B virus (HBV) genotypes B and C are common in Japan and have been demonstrated as one of the predictive factors associated with the progression of liver diseases. The aim of this study was to examine the changes over time in genotypes of HBV carriers in the hyperendemic area for HBV genotype B infection in Japan as well as in genotypes responsible for acute hepatitis B. Methods: We evaluated HBV genotypes in 430 HBsAg-positive HBV carriers and 34 patients with acute hepatitis B who had a medical examination at our university hospital between 1990 and 2010. The subjects were divided into two time-period groups (1990-1999 and 2000-2010) and analyzed the distribution of genotypes. In addition, the clinical and virological characteristics; ALT value, HBeAg, antiHBe antibody, IgM-HBc antibody, HBVDNA, were compared between subjects with genotype A infection and those with non-genotype A infection. Results: Of the 430 HBsAg-positive carriers, 45% had genotype B and 35% had genotype C in both time-period groups, indicating no changes in genotypes over time. Among 34 acute hepatitis B patients, the prevalence of genotype B was lower in the 2000-2009 group (1/17; 5.9%) than in the 1990-1999 group (10/17; 58.8%, p=0.012), while that of genotype A tended to have increased from 11.8% (2/17) to 29.4% (5/17) in the last 10 years. One of 7 patients with acute HBV genotype A infection did not clear HBsAg and developed to chronic infection. When Kaplan-Meier analysis was used to compare HBsAg clearance phase between the patients with or without genotype A infection, the phase was significantly longer in the genotype A patients (49 wks vs. 8 wks; p < 0.05). HBV DNA negative phase was also significantly longer in the genotype A patients (45 wks vs. 4.9 wks; p < 0.05), while the both groups showed no difference in HBeAg negative phase, anti-HBe positive phase, IgM-HBc antibody negative phase, and ALT normalization period. Conclusion: In a hyperendemic area for HBV genotype B infection in Japan, there was no large change of HBV genotypic distribution in carriers, while genotype A infection was increased in acute hepatitis B in the last 10 years. Compared to patients with acute HBV non-genotype A infection, patients with genotype A infection took a longer duration for HBsAg clearance and for achievement of HBV DNA negative status. Infection became chronic in some of the patients with infected with genotype A, suggesting that genotype distribution in HBV carriers will change in Japan in the future. It is necessary to re-examine the nation-wide study of clinical course of acute hepatitis B patients, especially infected with genotype A.