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The increasing incidence of hepatitis C virus (HCV) infections underscores the need for an effective vaccine. Successful vaccines to other viruses generally depend on a long-lasting humoral response. However, data on the half-life of HCV-specific responses are lacking. Here we study archived sera and mononuclear cells that were prospectively collected up to 18 years after cure of chronic HCV infection to determine the role of HCV antigen in maintaining neutralizing antibody and B cell responses. We show that HCV-neutralizing activity decreases rapidly in potency and breadth after curative treatment. In contrast, HCV-specific memory B cells persist, and display a restored resting phenotype, normalized chemokine receptor expression and preserved ability to differentiate into antibody-secreting cells. The short half-life of HCV-neutralizing activity is consistent with a lack of long-lived plasma cells. The persistence of HCV-specific memory B cells and the reduced inflammation after cure provide an opportunity for vaccination to induce protective immunity against re-infection.

Chronic hepatitis B infection remains a significant cause of morbidity and mortality worldwide despite the availability of an effective vaccine. The clinical management of chronic hepatitis B infection is complex often requiring the use of nucleotide analogs as well as immune modulators. The natural history and response to therapy are affected by the presence of naturally occurring mutations in the HBV genome particularly those in the basal core promoter and precore sites. Understanding the role of these mutations in outcome of infection and response to therapy can enable physicians to customize management in order to achieve optimal clinical outcomes.

BACKGROUND: Despite appropriate immunoprophylaxis, up to 10% of infants born to highly viremic hepatitis B virus (HBV–DNA C 7 log IU/mL) mothers are infected with HBV. Use of TDF to prevent vertical transmission (VT) by such mothers has not been evaluated. PURPOSE: To evaluate the efficacy and safety of TDF in preventing VT from highly viremic HBV-infected mothers. METHODS: Data were collected retrospectively from HBV mono-infected, hepatitis B e antigen (HBeAg) positive, pregnant women between 6/2008 and 11/2010. Cases enrolled were HBV mono-infected mothers who received TDF (300 mg orally once a day) in the third trimester. Those with pregnancy complications or an abnormal fetus on sonography were excluded from use of TDF. All infants received hepatitis B immunoglobulin and vaccination at birth and subsequently. RESULTS: Eleven Asian mothers received TDF at the median gestational age of 29 (28–32) weeks and the median duration of TDF use before delivery was 10 (7–12) weeks. A significant reduction in serum HBV–DNA was achieved at delivery compared with baseline (mean 5.25 ± 1.79 vs. 8.87 ± 0.45 log(10) copies/mL, respectively; p

Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B refers to an atypical presentation of chronic hepatitis B characterized by the absence of HBeAg but with clinical and histologic evidence of chronic hepatitis and the presence of ongoing viral replication. It is caused by a variety of mutations affecting transcription and translation of the precore-core RNA, the most common being the precore and double core promoter mutations. They have a worldwide distribution and development of the precore variant is genotype dependent. These variants may present as fulminant hepatitis but more commonly present as asymptomatic hepatitis during the natural course of chronic infection. The most characteristic pattern is one of severe flares followed by remissions. Long-term response to therapy is poor.

Chronic liver disease due to hepatitis C virus (HCV) infection is a major problem in hemophiliacs. Recent reports suggested that hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus (HIV) have an increased incidence of liver failure but the mechanism of accelerated liver injury is not clear. We tested plasma from 100 hemophiliacs for anti-HCV by second generation ELISA, anti-HIV by EIA, and HCV RNA and HIV RNA by branched DNA and polymerase chain reaction assays to determine if hemophiliacs coinfected with HCV and HIV have higher HCV RNA levels and more active liver disease. Seventy-nine (79%) patients were anti-HCV positive, of whom 85% were HCV RNA positive. None of the anti-HCV-negative patients had detectable HCV RNA in plasma. Forty-two (42%) patients were anti-HIV positive, of whom 47% had detectable HIV RNA. All the anti-HIV-positive patients were also anti-HCV positive. The prevalence of both anti-HCV and anti-HIV increased significantly with age. There was no difference in HCV RNA levels between anti-HIV-positive and anti-HIV-negative patients (mean: 21 +/- 4 vs 18 +/- 5 Meq/ml), although HCV RNA levels were significantly higher in anti-HIV-positive patients with CD4 counts200/mm3 (P = 0.008). There was an inverse correlation between HCV RNA levels and CD4 counts but no correlation was found between HCV RNA and serum aminotransferase levels. We found a high prevalence of HCV and HIV coinfection in our hemophiliacs. Hepatitis C virus replication appears to be increased in patients with severe immunodeficiency secondary to progressive HIV infection. However, there was no correlation between HCV RNA and serum ALT level, suggesting that HCV is not directly cytopathic.