Antiviral therapy and resistance with hepatitis B virus infection

Hepatitis B virus (HBV) infection is still the most com- mon cause of hepatocellular carcinoma and liver cirrho- sis world wide. Recently, however, there has been quite dramatic improvement in the understanding of HBV as- sociated liver disease and its treatment. It has become clear that high viral replication is a major risk factor for the development of both cirrhosis and hepatocellular carcinoma. Early studies have shown lamivudine low- ers the risk of HBV associated complications. There are currently three nucleos(t)ides licensed, in addition to interferon, and there are more drugs coming to the mar- ket soon. Interferon or its pegylated counterpart are still the only options for treatment with defined end points, while nucleos(t)ides therapy is used mostly for long term treatment. Combination therapies have not been shown to be superior to monotherapy in na?ve patients, how- ever, the outcome depends on how the end point is de- fined. Interferon plus lamivudine achieves a higher viral suppression than either treatment alone, even though Hbe-seroconversion was not different after a one year treatment. HBV-genotypes emerge as relevant factors, with genotypes "A" and "B" responding relatively well to interferon, achieving up to 20% HBsAg clearance in the case of genotype "A". In addition to having a defined treatment duration, interferon has the advantage of lack- ing resistance selection, which is a major drawback for lamivudine and the other nucleos(t)ides. The emergence of resistance against adefovir and entecavir is some- what slower in na?ve compared to lamivudine resistant patients. Adefovir has a low resistance profile with 3%, 9%, 18%, and 28% after 2, 3, 4, and 5 years, respec- tively, while entecavir has rarely produced resistance in na?ve patients for up to 3 years.

Hepatitis C virus core antigen testing: Role in diagnosis, disease monitoring and treatment

While hepatitis B virus(HBV)screening relies on hepatitis B surface antigen to confirm HBV infection since the early days of hepatitis B disease management,hepatitis C virus(HCV)infection screening is based on anti-HCV testing which does not discriminate active from past infection.Thus to confirm infection HCV RNA testing has been required;recently a HCV core antigen assay became widely commercially available which could serve to confirm infection.That assay is less sensitive than current HCV RNA assays,but as more than 50%of anti-HCV positive persons will be HCV core antigen positive,HCV core antigen testing can be a cost effective and reflex test to confirm HCV infection in anti-HCV positive individuals and will be easier as it can be applied on the same platform.For treatment monitoring,more data need to be generated,but the early data available at present suggest that HCV core antigen may be an alternative to HCV RNA monitoring.With direct antivirals,HCV core antigen could even be superior to HCV RNA testing,as direct antivirals might already prevent virus formation when HCV core antigen is still produced and thereby correlates better with eventual viral clearance.

Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration

AIM: To evaluate pretreatment hepatitis B virus(HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement.METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration(VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment(2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status(from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during antiCD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV(hepatitis B surface antigen positive or HBs Ag+), past HBV(HBs Ag-, hepatitis B core antibody positive or HBc Ab+), resolved HBV(HBs Ag-, HBc Ab+, hepatitis B surface antibody positive or HBs Ab+), likely prior vaccination(isolated HBs Ab+), HBV negative(HBs Ag-, HBc Ab-), or unknown. Acute hepatitis B was defined by the appearance of HBs Ag+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group.RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224(53%) had pretreatment HBs Ag testing during the study period, with 49% and 43% tested for HBs Ag and HBc Ab, respectively within 6 mo pretreatment in 2014. Of those tested, 2%(167/10224) had chronic HBV, 4%(326/7903) past HBV, 5%(427/8110) resolved HBV, 8%(628/8110) likely prior HBV vaccination, and 76%(6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative(P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16(0.3%) developed acute hepatitis B of 4947 tested during anti-CD20 Ab treatment and followup. CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.