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Chronic hepatitis B is a numerically important cause of cirrhosis and hepatocellular carcinoma. Nucleoside analogue therapy may modify the risk. However, maintenance suppressive therapy is required, as a functional cure (generally defined as loss of HBsAg off treatment) is an uncommon outcome of antiviral treatment. Chronic hepatitis B is a numerically important cause of cirrhosis and hepatocellular carcinoma. Nucleoside analogue therapy may modify the risk. However, maintenance suppressive therapy is required, as a functional cure (generally defined as loss of HBsAg off treatment) is an uncommon outcome of antiviral treatment. Currently numerous investigational agents being developed to either interfere with specific steps in HBV replication or as host cellular targeting agents, that inhibit viral replication, and deplete or inactivate cccDNA, or as immune modulators. Synergistic mechanisms will be needed to incorporate a decrease in HBV transcription, impairment of transcription from HBV genomes, loss of cccDNA or altered epigenetic regulation of cccDNA transcription, and immune modulation or immunologically stimulated hepatocyte cell turnover. Nucleoside analogue suppressed patients are being included in many current trials. Trials are progressing to combination therapy as additive or synergistic effects are sought. These trials will provide important insights into the biology of HBV and perturbations of the immune response, required to effect HBsAg loss at different stages of the disease. The prospect of cures of hepatitis B would ensure that a wide range of patients could be deemed candidates for treatment with new compounds if these were highly effective, finite and safe. Withdrawal of therapy in short-term trials is challenging because short-term therapies may risk severe hepatitis flares, and hepatic decompensation. The limited clinical trial data to date suggest that combination therapy is inevitable.

Instruments to assess the impact of hepatitis C virus infection on health and measurements of reported outcomes in patients (health-related quality of life [HRQOL]) are not frequently used to assign priority for treatment. Several systematic reviews have been performed that provide a comprehensive analysis to help understand patient reported outcomes (PROs) with direct acting antiviral treatment. Clinical trials with direct acting antivirals (DAAs) provide an important opportunity to assess PROs without interferon or ribavirin. Significant improvement in quality of life parameters have been noted with DAA therapy. The results show improvement in HRQOL indices when interferon-free and particularly interferon and ribavirin-free treatments are compared to interferon and ribavirin treatment. Improvements in HRQOL indices are an encouraging aspect of the cure of chronic hepatitis C. It is unclear whether these measurable HRQOL improvements can be translated into a net benefit improvement in work productivity and a social dimension that is significant enough to convince payers of the added value of early and more widespread treatment.

Background & Aims We evaluated the antiviral response of Asian or Pacific Islander (API) patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as pre-treatment hepatitis B virus (HBV) DNA ≥9 log10 copies/ml, following up to 288 weeks of tenofovir disoproxil fumarate (TDF) treatment. Methods A total of 205 HBeAg-negative and HBeAg-positive self-described API patients received 48 weeks of TDF 300 mg (HVL n = 18) or adefovir dipivoxil 10 mg (HVL n = 15) in a blinded fashion, followed by open-label TDF for an additional 240 weeks. The proportions of HVL vs. non-HVL patients with HBV DNA

In 2010, the World Health Assembly adopted a resolution calling for interventions for the prevention and control of chronic viral hepatitis. These infectious diseases mostly affect resource-limited countries accounting for 80% of the world's population and facing numerous obstacles to contain the epidemic. At a time when morbidity and mortality of chronic liver disease have been considerably improved in wealthy countries by new innovative strategies and new potent antiviral drugs, it is now urgent to recall for concrete actions from stakeholders of global health policy to reduce the burden in resource-limited countries.

Weekly injections with pegylated-IFNa (PegIFN) combined with daily ribavirin (RBV) are still the standard of care for chronic hepatitis C in most of the world. Sustained virological response (SVR) of 40-50% for patients infected with HCV genotypes (GT) 1 or 4 and 70-90% for genotypes 2-3 are achieved with this regimen. Triple therapy, registered in both the EU and USA, utilizing the first-generation direct protease inhibitors is able to increase the SVR rates to 75%, but its use is restricted to patients infected with HCV GT1. Additional limitations include challenging dosing schedules, complex treatment algorithms, limited efficacy in patients with previous null response to PegIFN/RBV therapy and additional side effects. There is also an important need for more effective antiviral therapy for difficult-to-treat populations with PEG-IFN intolerance, particularly those with cirrhosis and non-responders to previous therapies. All-oral, IFN-free therapies are an evolutionary step for future anti-HCV therapies. Initial results of clinical studies conducted during the last year give hope for 'a pill for HCV' at least in selected CHC populations. In 2013 several clinical trials of all-oral anti-HCV therapies had been completed, first all-oral combination submitted for registration and some conclusions could be drawn. However, there is not yet a clear direction for IFN-free therapies in treatment naïve patients or more complex non-responders.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with chronic progressive liver disease. Its global epidemiology is still not well ascertained and its impact will be confronted with a higher burden in the next decade. AIM: The goal of this study was to develop a tool that can be used to predict the future prevalence of the disease in different countries and, more importantly, to understand the cause and effect relationship between the key assumptions and future trends. METHODS: A system approach was used to build a simulation model where each population was modeled with the appropriate inflows and outflows. Sensitivity analysis was used to identify the key drivers of future prevalence. RESULTS: The total HCV-infected population in the US was estimated to decline 24% from 3.15 million in 2005 to 2.47 million in 2021, while disease burden will increase as the remaining infected population ages. During the same period, the mortality rate was forecasted to increase from 2.1 to 3.1%. The diagnosed population was 50% of the total infections, while less than 2% of the total infections were treated. CONCLUSION: We have created a framework to evaluate the HCV-infected populations in countries around the world. This model may help assess the impact of policies to meet the challenges predicted by the evolution of HCV infection and disease. This prediction tool may help to target new public health strategies.

Hepatitis C virus (HCV) genotypes 4, 5 and 6 represent20% of all HCV cases worldwide. HCV-4 is mainly seen in Egypt, where it represents 90% of all HCV cases. Antischistosomal therapy was the main cause of contamination there, followed by procedures performed by informal providers and traditional healers such as dental care, wound treatment, circumcision, deliveries, excision and scarification. It is also highly prevalent in sub-Saharan Africa and in the Middle East. In Europe, its prevalence has recently increased particularly among intravenous drug users and in immigrants. HCV-5 is mainly found in South Africa, where it represents 40% of all HCV genotypes, but four pockets of HCV-5 were found in France, Spain, Syria and Belgium and sporadic cases were found elsewhere. The mode of transmission is mainly iatrogenic and transfusion. HCV-6 is found in Hong Kong, Vietnam, Thailand and Myanmar and also in American and Australian from Asian origin. The response to treatment in HCV-4 is intermediate between HCV-1 and HCV-2 and HCV-3. A sustained viral response is achieved in 43-70% with pegylated interferon and ribavirin. It is higher in Egyptians than Europeans and Africans and is negatively related to insulin resistance and to the severity of fibrosis. It increases to80% with 24 weeks of therapy only if a rapid virological response is achieved. In HCV-5, a sustained virological response is achieved in60% with 48 weeks of therapy. HCV-6 is also considered an easy-to-treat genotype, leading to a response in 60-85% of cases.

Background: Current oral therapy for hepatitis B virus (HBV) is limited by the presence of resistance leading to resumption of higher levels of HBV replication. Therefore, there is a need for a better definition of the potential role and limitations of lamivudine or similar therapies, used alone. Aims: To examine the viability of lamivudine and similar monotherapies as a treatment strategy in chronic HBV in the face of the worldwide burden of disease. Methods: We have reviewed the role of lamivudine monotherapy in the treatment of chronic HBV in a single tertiary referral liver centre over a 9-year period. We analysed the outcome in 90 patients where lamivudine has apparently conferred long-term viral suppression and investigated the development of genotypic resistance in the absence of ostensible phenotypic resistance. Patients were subdivided into hepatitis B e antigen (HBeAg)-positive and anti-HBe-positive groups. Results: Virtually all HBeAg-positive patients who failed to seroconvert have progressed to combination antiviral therapy. Only 19%(7/36) of HBeAg-negative patients have continued suppression without detectable genotypic change after 4 years of therapy. Conclusions: These data demonstrate that despite a relatively low level of viraemia in HBeAg-negative patients, we could detect resistance mutations by direct sequencing in all patients with amplifiable HBV DNA. Our results suggest that for patients with ongoing replication at ‘amplifiable’ levels of HBV DNA, but